Radioisotope delivery system with multiple detectors to detect gamma and beta emissions

ABSTRACT

A nuclear medicine infusion system ( 10 ) may be used to generate and infuse radioactive liquid into a patient undergoing a diagnostic imaging procedure. In some examples, the infusion system includes a frame ( 30 ) that carries a radioisotope generator ( 52 ) that generates radioactive eluate via elution. The frame may also carry a beta detector ( 58 ) and a gamma detector ( 60 ). The beta detector can be positioned to measure beta emissions emitted from the radioactive eluate supplied by the generator. The gamma detector can be positioned to measure gamma emissions emitted from a portion of the radioactive eluate to evaluate a safety of the radioactive eluate delivered by the infusion system.

CROSS-REFERENCE

This application is a 35 U.S.C. 371 national phase filing fromInternational Application No. PCT/US2017/052535, filed Sep. 20, 2017,which claims the benefit of U.S. Provisional Patent Application No.62/397,022, U.S. Provisional Patent Application No. 62/397,025, and U.S.Provisional Patent Application No. 62/397,026, each of which was filedon Sep. 20, 2016. The entire contents of these applications areincorporated herein by reference.

TECHNICAL FIELD

This disclosure relates to radiopharmaceuticals used in nuclear medicineand, more particularly, to systems and techniques for generating anddelivering radiopharmaceuticals.

BACKGROUND

Nuclear medicine employs radioactive material for therapy and diagnosticimaging. Positron emission tomography (PET) is one type of diagnosticimaging, which utilizes doses of radiopharmaceutical. The doses ofradiopharmaceutical may be injected or infused into a patient prior toor during a PET scan procedure. An infused dose of radiopharmaceuticalcan be absorbed by cells of a target organ of the patient and emitradiation. A PET scanner can detect the emitted radiation in order togenerate an image of an organ. For example, to image body tissue such asthe myocardium, a patient may be injected or infused with rubidium-82(⁸²Rb). Rubidium-82 may exhibit similar physiological uptake aspotassium and, accordingly, may be taken into the myocardium followingpotassium pathways.

Rubidium-82 can be generated for nuclear medicine procedures using astrontium-rubidium generator (⁸²Sr/⁸²Rb generator). Rubidium-82 is aradioactive decay product of strontium-82. Typically, strontium-rubidiumgenerators contain strontium bound to a generator column through whichan eluant is flushed during operation. As strontium-82 decays torubidium-82, the rubidium-82 may release from the generator column andenter the eluant. The resulting stream, which is called an eluate, canbe injected or infused into a patient.

SUMMARY

In general, the disclosure is directed to devices, systems, components,and techniques for generating and/or delivering radioactive liquids. Theradioactive liquid may be generated and infused into a patient during adiagnostic imaging procedure, such as a positron emission tomography(PET)/computed tomography (CT) or a positron emission tomography(PET)/magnetic resonance imaging (MRI) procedure. Before, during, and/orafter a specific diagnostic imaging procedure, the radiation level ofradioactive liquid generated by an infusion system may be measured todetermine the activity level (e.g., magnitude of radiation emissions) ofone or more radioisotope in the radioactive liquid. The activity levelof one or more radioisotopes may be measured to determine that aradioisotope targeted for infusion into a patient during an imagingprocedure is at an appropriate level for the specific procedure beingundertaken. Additionally or alternatively, the activity level of one ormore radioisotopes may be measured to determine if a radioisotope havinga longer half-life than the radioisotope targeted for infusion ispresent above a threshold concentration in the radioactive liquid. Suchcomparatively long-lasting radioisotopes may be contaminants that aredesirably excluded from infusion into a patient.

For example, in the application of a strontium-rubidium radioisotopegenerator, a radioactive eluate containing the radioisotope rubidium-82(also referred to as ⁸²Rb and Rb-82) can be generated by passing aneluant across a substrate containing bound strontium-82 (also referredto as ⁸²Sr and Sr-82). As Sr-82 decays into Rb-82, the Rb-82 may releasefrom the substrate, causing the Rb-82 to release into the eluant andthereby generating a radioactive eluate via elution. As the radioisotopegenerator approaches the end of its service life, strontium may itselfbegin releasing into the eluate produced by the generator in addition toits decay product Rb-82. The activity level of strontium in the eluatemay be monitored to help ensure that eluate containing too muchstrontium (or other contaminating radioisotope) is not injected into thepatient. This is because Sr-82 has a much longer half-life (25.5 days)than the half-life of Rb-82 (76 seconds) and, if injected into thepatient, will produce radioactive emissions inside of patient for alonger period of time than Rb-82.

In some examples according to the present disclosure, an infusion systemis described that includes multiple detectors positioned to evaluate thesafety of radioactive eluate generated by a radioisotope generator. Themultiple detectors may each be used to determine the activity of thesame or different radioisotopes in the radioactive eluate. Each detectorcan detect radioactive emissions emitted from the radioactive eluate,and the activity level, or concentration, of one or more radioisotopesthat may be present in the radioactive eluate can be determinedtherefrom. In some configurations, the multiple detectors areimplemented using a beta detector and a gamma detector.

A beta detector can measure beta emissions caused by radioactive betadecay. During beta decay, a beta particle that is either an electron ora positron is emitted from an atomic nucleus. The beta detector candetect beta particles emitted from the radioactive eluate, allowing theactivity level of a radioisotope assumed to be associated with thosebeta particles to be determined. By contrast, the gamma detector canmeasure gamma emissions or photons caused by radioactive gamma decay.During gamma decay, a stream of high-energy photons may be emitted froman atomic nucleus, providing detectable gamma rays. The energy level ofthe gamma rays may vary depending on the specific radioisotope fromwhich the rays are emitted. The gamma detector can detect the gammaemissions, for example by measuring a full or partial gamma spectrum,allowing the activity level of one or more radioisotopes to bedetermined. A gamma detector can discriminate photons with differentenergy levels, unlike a dose calibrator.

Activity measurements made by a beta detector and a gamma detector aredistinguishable from activity measurements made by a dose calibrator. Adose calibrator is an instrument used to assay the activity of aradioactive material prior to clinical use. The objective of the assayis to assure that the patient receives the prescribed dose for thediagnostic or therapeutic purpose. A dose calibrator includes anelectrometer designed to measure a wide range of ionization current,spanning from femtoamperes (fA) for beta emitters up to tens ofpicoamperes (pA) for high-energy, high-yield photon emitters. Somehigh-activity assays can even involve microamperes (pA) currents. Theaccuracy of the electrometer depends upon the type and quality of theelectrometer and the accuracy of the standard reference sources used tocalibrate the electrometer. Dose calibrators have no intrinsic photonenergy discrimination capability. A dose calibrator does not include aspectrometer and does not restrict the measurement to specific photonenergies to the exclusion of others, which a gamma detector is capableof performing.

While the configuration of the radioisotope generator system can vary asdescribed herein, in some examples, the system includes a beta detectorpositioned to measure the radioactivity of eluate flowing through tubingpositioned adjacent the beta detector. The gamma detector may also bepositioned to measure the radioactivity of eluate flowing through tubingor may instead be positioned to measure the radioactivity of a static(non-flowing) portion of radioactive eluate positioned adjacent thegamma detector. For example, the radioisotope generator system mayinclude an eluate-receiving container in fluid communication with anddownstream of infusion tubing in fluid communication with the outlet ofa radioisotope generator. Radioactive eluate generated by theradioisotope generator can flow through the tubing and past the betadetector before discharging into the eluate-receiving containerpositioned adjacent the gamma detector.

The radioisotope generator system may operate in different modes inwhich measurements from the beta detector and/or the gamma detector aremade. For example, during a quality control procedure, an infusiontubing line in fluid communication with the outlet of the radioisotopegenerator may be attached to the eluate-receiving container instead of apatient catheter. During this quality control procedure, theradioisotope generator may produce radioactive eluate that flows throughthe tubing line, past the beta detector, and into the eluate-receivingcontainer. The beta detector may measure beta emissions from theradioactive eluate as it flows through the infusion tubing, e.g., todetermine an activity level of Rb-82 in the eluate. The gamma detectormay receive gamma emissions from eluate in the eluate-receivingcontainer, e.g., to determine an activity level of Sr-82, strontium-85(also referred to as ⁸⁵Sr or Sr-85), and/or other contaminants in theeluate.

In practice, the activity level of Rb-82 in the eluate flowing throughthe infusion tubing line may be an order of magnitude or more greaterthan the activity level of any contaminants in the eluate. Accordingly,all beta emissions measured by the beta detector (including thoseemitted from Rb-82 and any potential contaminants, such as strontium)may be assumed to be emitted from Rb-82 present in the eluate withoutresolving those emissions emitted from any contaminating isotopes. Todetermine the activity of any such contaminating isotopes, the gammaemissions from a static portion of eluate in the eluate-receivingcontainer can be measured. In some applications, the eluate is held inthe eluate-receiving container for a period of time sufficient to allowRb-82 in the eluate to substantially decay. This can reduce the amountof interfering gamma radiation (from Rb-82) measured by the gammadetector and allow the gamma detector to better detect gamma radiationemitted from contaminating radioisotopes (e.g., strontium). The activitylevel of one or more such contaminating radioisotopes can be determinedbased on the measured gamma emissions. If the activity of one or moresuch contaminating radioisotopes exceeds an allowable limit, theradioisotope generator system can prohibit a subsequent patient infusionprocedure.

In addition to operating in a quality control mode, the radioisotope canalso operate in a patient infusion mode to perform a patient infusionprocedure. During the patient infusion procedure, the infusion tubingline in fluid communication with the outlet of the radioisotopegenerator may be attached to a patient catheter. Radioactive eluategenerated by the radioisotope generator can flow through the tubing andpast the beta detector. The radioisotope generator system may determine,based on the level of beta emissions measured by the beta detector, theactivity of Rb-82 in the eluate produced by the radioisotope generator.The radioisotope generator system may divert eluate initially producedby the generator to a waste container until a threshold amount of Rb-82activity is detected in the eluate. Upon detecting a threshold amount ofRb-82 activity via the beta detector, the generator system may divertthe eluate from the waste container to the patient catheter, therebyinjecting or infusing the patient with the eluate containing theradioactive Rb-82.

By configuring the radioisotope generator system with both a betadetector and a gamma detector, the radioisotope generator system canprovide an integrated system to help ensure the safety and accuracy ofradioactive eluate generated by the system. The combination of detectorscan be used to perform a variety of different radioisotope measurementsand to implement corresponding control schemes and/or quality analysesbased on those radioisotope measurements. Accordingly, configuring thesystem with multiple detectors (e.g., measuring different types ofradioactive emissions) may provide more accurate resolution betweendifferent radioisotopes and/or allow activities determined usingmultiple detectors to be cross-checked for increased accuracy.

In some examples, a radioisotope generator system according to thedisclosure is configured as a mobile cart carrying a beta detector, agamma detector, a radioisotope generator, a controller, and associatedhardware and software to execute the techniques describes herein. Theradioisotope generator system may also include a shielding assembly thatprovides a barrier to radioactive radiation. The shielding assembly canbe mounted on the mobile cart and one or more of the other componentscarried on the cart can be mounted in the shielding assembly.

In some configurations, the shielding assembly includes a plurality ofcompartments separated by one or more walls of shielding material. Forexample, the shielding assembly may include one compartment containingthe radioisotope generator and another compartment containing the gammadetector. The compartments of the shielding assembly can be arranged toposition the compartment containing the gamma detector relative to thecompartment containing the radioisotope generator so as to reducebackground radiation emitted by the radioisotope generator from beingdetected by the gamma detector. If the gamma detector is exposed to toomuch background radiation (e.g., radiation emitted by the contents ofthe generator column), the gamma detector may be saturated and/or unableto suitably detect the level of radiation emitted by an eluate samplepositioned in front of the detector when evaluating the safety of theeluate. Accordingly, ensuring that the gamma detector is appropriatelyshielding from the radioisotope generator may help ensure the safe andefficacious operation of the entire radioisotope generator system.

In one example, an infusion system is described that includes a framethat carries a beta detector and a gamma detector and is furtherconfigured to receive a radioisotope generator that generatesradioactive eluate via elution. The beta detector is positioned tomeasure beta emissions emitted from the radioactive eluate. The gammadetector is positioned to measure gamma emissions emitted from a portionof the radioactive eluate to evaluate the safety of the radioactiveeluate delivered by the infusion system, e.g., in addition to performingother functions such as dose constancy (which may also be referred to asa constancy evaluation or constancy check).

In another example, an infusion system is described that includes a betadetector, a gamma detector, a radioisotope generator, a waste container,an eluate-receiving container, and an infusion tubing line. The betadetector is positioned to measure beta emissions emitted fromradioactive liquid supplied by the radioisotope generator and flowingthrough the infusion tubing line. The gamma detector is positioned tomeasure gamma emissions emitted from a static volume of radioactiveliquid received by the eluate-receiving container.

In another example, an infusion system is described that includes amovable frame, an eluant reservoir, a pump, and a radioisotope generatorcoupled to the eluant reservoir through the pump. The radioisotopegenerator is configured to generate radioactive eluate containing Rb-82via elution of a column containing Sr-82. The example specifies that theinfusion system also includes a waste container, an eluate-receivingcontainer, and an infusion tubing circuit. The infusion tubing circuitincludes an infusion tubing line, an eluate line, and a waste line. Theeluate line is connected to an outlet of the radioisotope generator, thepatent line is positioned to provide fluid communication between theeluate line and the eluate-receiving container, and the waste line ispositioned to provide fluid communication between the eluate line andthe waste container. The example also includes a beta detector and agamma detector. The beta detector is positioned to measure betaemissions emitted from radioactive eluate generated by the radioisotopegenerator and flowing through the eluate line. The gamma detector ispositioned to measure gamma emissions emitted from radioactive eluategenerated by the radioisotope generator and received by theeluate-receiving container.

In another example, an infusion system is described that includes amovable frame, an eluant reservoir, a pump, and a radioisotope generatorcoupled to the eluant reservoir through the pump. The radioisotopegenerator is configured to generate radioactive eluate containing Rb-82via elution of a column containing Sr-82. The example specifies that thesystem also includes a waste container, an eluate-receiving container,and an infusion tubing circuit. The infusion tubing circuit includes aninfusion tubing line, an eluate line, and a waste line. The eluate lineis connected to an outlet of the radioisotope generator, the patent lineis positioned to provide fluid communication between the eluate line andthe eluate-receiving container, and the waste line is positioned toprovide fluid communication between the eluate line and the wastecontainer. The example system also includes radioactive shielding, abeta detector, and a gamma detector. The radioactive shield encloses atleast a portion of the infusion tubing circuit, the beta detector, andthe gamma detector. The beta detector is positioned to measure betaemissions emitted from radioactive eluate generated by the radioisotopegenerator and flowing through the eluate line. The gamma detector ispositioned to measure gamma emissions emitted from radioactive eluategenerated by the radioisotope generator and received by theeluate-receiving container. The system also includes a controller inelectronic communication with the beta detector and the gamma detector.The controller is configured to determine an activity of Rb-82 in theradioactive eluate based on beta emissions measured by the beta detectorand determine an activity of Sr-82 and/or Sr-85 in the radioactiveeluate based on gamma emissions measured by the gamma detector (e.g., bymeasuring gamma emissions from the decay product of Sr-82, Rb-82). Thecontroller is further configured to control the infusion system todeliver a dose of the radioactive eluate to a patient during a patientinfusion procedure.

In another example, a system is described that includes a shieldingassembly that has a plurality of compartments each providing a barrierto radioactive radiation. The system includes a first compartmentconfigured to receive a radioisotope generator that generates aradioactive eluate via elution, a second compartment configured toreceive a beta detector, and a third compartment configured to receive agamma detector.

In another example, a system is described that includes a shieldingassembly that includes a plurality of compartments each providing abarrier to radioactive radiation. The system includes a firstcompartment configured to receive and hold a radioisotope generator thatgenerates a radioactive eluate via elution and a second compartmentconfigured to receive a beta detector and at least a portion of aninfusion tubing circuit that is in fluid communication with theradioisotope generator. The example specifies that the beta detector ispositioned to measure beta emissions emitted from radioactive eluategenerated by the radioisotope generator and flowing through the portionof the infusion tubing circuit. The system also includes a thirdcompartment configured to receive an eluate-receiving container and agamma detector. The gamma detector is positioned to measure gammaemissions emitted from a static portion of the radioactive eluatereceived by the eluate-receiving container. In addition, the examplestates that the system includes a fourth compartment configured toreceive a waste container.

In another example, an infusion system is described that includes aframe that carries a beta detector, a gamma detector, and a controllercommunicatively coupled to the beta detector and the gamma detector. Theframe is further configured to receive a strontium-rubidium radioisotopegenerator that generates a radioactive eluate via elution. The examplespecifies that the beta detector is positioned to measure beta emissionsemitted from the radioactive eluate and the gamma detector is positionedto measure gamma emissions emitted from the radioactive eluate. Theexample also specifies that the controller is configured to determine anactivity of rubidium in the radioactive eluate based on the betaemissions measured by the beta detector and determine an activity ofstrontium in the radioactive eluate based on the gamma emissionsmeasured by the gamma detector.

In another example, a method is described that includes pumping aneluant through a strontium-rubidium radioisotope generator and therebygenerating a radioactive eluate via elution. The method involvesconveying the radioactive eluate across a beta detector and measuringbeta emissions emitted from the radioactive eluate generated by theradioisotope generator and flowing through an eluate line anddetermining therefrom an activity of the radioactive eluate. The methodalso involves receiving the radioactive eluate conveyed across the betadetector in an eluate-receiving container positioned adjacent a gammadetector. In addition, the method includes measuring gamma emissionsemitted from the radioactive eluate received by the eluate-receivingcontainer and determining therefrom an activity of strontium in theradioactive eluate in the eluate-receiving container.

The details of one or more examples are set forth in the accompanyingdrawings and the description below. Other features, objects, andadvantages will be apparent from the description and drawings, and fromthe claims.

BRIEF DESCRIPTION OF DRAWINGS

FIGS. 1 and 2 are perspective and top views, respectively, of an exampleinfusion system that can be used to generate and infuse radioactiveliquid.

FIG. 3 is a rear view of the system shown in FIGS. 1 and 2 illustratingadditional example features that can be included in the system.

FIGS. 4 and 5 are perspective and top views, respectively, of the systemof FIGS. 1-3 shown with the cabinet structure removed for purposes ofillustration and illustrating an example shielding assembly arrangement.

FIG. 6 is a block diagram illustrating an example arrangement ofcomponents that can included in the system of FIGS. 1-5 to generateradioactive eluate and detect radioactive emissions.

FIGS. 7A and 7B are perspective views of an example configuration of theshielding assembly from FIGS. 4 and 5 shown removed from the cart framefor purposes of illustration.

FIG. 7C is a perspective view of the example shielding assembly fromFIGS. 7A and 7B shown sectionalized along the A-A sectional lineindicated on FIG. 7A.

FIG. 7D is a side view of the example shielding assembly from FIGS. 7Aand 7B shown sectionalized along the B-B sectional line indicated onFIG. 7A.

FIG. 7E is a top view of the example shielding assembly from FIGS. 7Aand 7B illustrating an example arrangement of compartments in which aradiation path passes through one or more sidewall sections defining thecompartments.

FIG. 7F is exploded view of a portion of the example shielding assemblyfrom FIG. 7D showing an example arrangement of an eluate-receivingcontainer relative to a gamma detector.

FIG. 8 is a flow diagram of an example technique that may be used toperform a patient infusion procedure to infuse radioactive liquid into apatient.

FIG. 9 is a flow diagram of an example technique that may be used toperform a quality control procedure.

FIGS. 10-16 describe exemplary calibration and quality control test thatmay be periodically performed on an infusion system according to thedisclosure.

DETAILED DESCRIPTION

In general, the disclosure relates to systems, components, andtechniques for generating radioactive liquids, infusing radioactiveliquids into patients, and ensuring the safety, accuracy, and quality ofthe radioactive liquids so generated. The described systems, components,and techniques can be implemented to detect and quantify multipledifferent radioisotopes. In some examples, a system includes multipledetectors positioned at different locations along the fluid pathway froma radioisotope source to measure one or more radioisotopes present inthe fluid provided by the radioisotope source. The radioactive emissionsdetected and measured by the multiple detectors, alone or incombination, can be used to determine the activity of one or moreradioisotopes present in the system. If the system determines that theactivity of one or more radioisotopes is within allowable limits, thesystem may permit and control delivery of radioactive liquid from theradioisotope source to a patient. By contrast, if the system determinesthat the activity of one or more radioisotopes is outside of anallowable limit, for example during a quality control procedure, thesystem may prevent infusion into a patient during a subsequent patientinfusion procedure until the issue is resolved.

In some examples described herein, a radioisotope generator systemincludes a beta detector and a gamma detector positioned downstream ofthe radioisotope generator that generates radioactive eluate viaelution. During a patient infusion procedure, an infusion tubing circuitcan connect an outlet of the radioisotope generator to a patientcatheter. The infusion tubing circuit can be positioned adjacent thebeta detector such that, as eluate flows through the infusion tubingcircuit, the eluate passes over the beta detector. Beta emissionsemitted by the eluate can be detected by the beta detector and theactivity of a radioisotope associated with those beta emissionsdetermined.

To execute a quality control procedure, the infusion tubing circuit canbe connected to an eluate-receiving container instead of a patientcatheter. The eluate-receiving container may be a vessel positionedadjacent to the gamma detector such that gamma emissions emitted byeluate received in the container can be detected by the gamma detector.During operation, an amount of eluate sufficient to partially or fullyfill the eluate-receiving container can be generated and supplied to theeluate-receiving container. The gamma detector can then measure gammaemissions emitted by the eluate in the receiving container, e.g., todetermine the activity of one or more radioisotopes present in theeluate. In some applications, beta emissions measured by the betadetector are used to determine the activity of Rb-82 in the eluate whilegamma emissions measured by the gamma detector are used to determine theactivity of contaminants such as strontium in the eluate.

A multi-detector system that facilitates measurement of different typesof radioactive decay products from the same radioactive liquid samplemay be integrated with the radioisotope generator that produces theradioactive liquid so measured. This can provide an integrated systemfor convenient use in, and deployment to, different clinical locations.For example, an integrated system, which may or may not be mobile, caninclude a frame that carries a beta detector and a gamma detector and isfurther configured to receive a radioisotope generator that generatesradioactive eluate via elution. The beta detector can be supported onthe frame either directly or indirectly, e.g., via radioactive shieldingmaterial. Similarly, the gamma detector can be supported on the frameeither directly or indirectly, e.g., also via radioactive shieldingmaterial. The beta detector and the gamma detector can be positioned tomeasure beta and gamma emissions, respectively, from radioactive eluatedischarged from the radioisotope generator. For example, the gammadetector can be positioned to measure gamma emissions from a portion ofthe radioactive eluate that allows for the safety of the radioactiveeluate delivered by the overall infusion system to be evaluated. Aninfusion system can have a variety of features, functionalities, andcomponents as described herein.

FIGS. 1 and 2 are perspective and top views, respectively, of an exampleinfusion system 10 that can be used to generate and infuseradiopharmaceutical liquid. In the illustrated example, system 10includes a cabinet structure 12 mounted on wheels 14 so as to bemovable. System 10 also includes a user interface 16 that can beelectronically and/or communicatively coupled to a controller thatcontrols the operation of the infusion system. As described in greaterdetail below, cabinet structure 12 may house a radioisotope generatorand multiple detectors configured to detect radioactive decay products,such as beta emissions and gamma emissions. In operation, theradioisotope generator may generate radioactive eluate via elution withan eluant. The eluate may be delivered proximate a beta detector tomeasure beta emissions emanating from the eluate and/or proximate agamma detector to measure gamma emissions emanating from the eluate. Acontroller associated with system 10 may control operation of the systembased on the measured beta emissions and/or measured gamma emissions.

Cabinet structure 12 may be a shell or a housing that defines aninterior space configured to contain various components of system 10.For example, cabinet structure 12 may be configured (e.g., sized and/orshaped) to contain a shielding assembly in which radioactive materialsof system 10 are contained, a pump to pump liquid through a radioisotopegenerator in the cabinet structure, a controller that controls operationof system 10, and/or other components of the system. Cabinet structure12 may be fabricated from durable polymeric materials, light weightmetals, or other suitable materials. In some examples, cabinet structureis fabricated from a radiation-resistant or impregnated polymericmaterial to prevent degradation of the cabinet structure in the eventthat radioactive liquid is inadvertently spilled on the cabinetstructure.

Cabinet structure 12 may include one or more openings, doors, and/orremovable portions to access an interior of the cabinet structure andcomponents contained therein. In the illustrated example, cabinetstructure 12 includes an opening 18 formed in the upper surface of thestructure through which a portion of a shielding assembly extends and isaccessible. As will be discussed in greater detail below, the portion ofthe shielding assembly extending through opening 18 may include a doorto access a compartment that receives a portion of an infusion tubingcircuit and/or a door to access a compartment into which aneluate-receiving container is inserted. As further illustrated, cabinetstructure 12 may include a removable portion 20 that can be removed froma remainder of the cabinet structure to access an interior of thestructure. In some examples, removable portion 20 provides access to adoor of a shielding assembly compartment containing a radioisotopegenerator.

In the example of FIGS. 1 and 2 , cabinet structure 12 is mounted onwheels 14. Wheels 14 may be useful to allow system 10 to be easily movedfrom one location to another location, e.g., to perform patient infusionprocedures in different locations or to perform maintenances or repairtasks. To prevent system 10 from inadvertently moving after beingpositioned in a desired location, the system may include a brake systemthat prevents the system from being moved when engaged. As shown in FIG.2 , system 10 includes a brake system the includes at least one peddlemounted at the rear end of the cabinet structure, which is illustratedas including a first peddle 20A to engage the brake system and a secondpeddle 20B to disengage the brake system. The peddles 20A and 20B can beoperatively connected to a mechanical interlock, friction pad, or otherstructure that, once engaged, inhibits movement of system 10. Pushingfirst peddle 20A downwardly with respect to gravity can engage the brakesystem while pushing second peddle 20B downwardly with respect togravity can disengage the brake system. In other configurations, system10 may only have a single break peddle that is pressed to both engageand disengage the break system, a hand control to engage and disengagethe break system, or yet other engagement feature. When configured withmultiple brake pedals as shown in FIG. 2 , the pedals can be colorindexed to indicate engagement (e.g., red for stop) and disengagement(e.g., green for go).

As mentioned above, system 10 also includes user interface 16. Userinterface 16 may include a display screen as illustrated or other outputmedia, and user input media. For example, user interface may include akeyboard, mouse, depressible buttons, switches, and/or touch screeninterface. In some examples, user interface 16 may be configured toprovide visual, audible, and/or tactile feedback to a user. Userinterface 16 may be communicatively coupled (e.g., via a wired orwireless connection) to a controller that controls the operation ofsystem 10. A clinician or other user may interact with system 10 throughuser interface 16, e.g., to change or establish the parameters of apatient infusion procedure, change or establish the parameters of aquality control procedure, view historical or maintenance information,or otherwise interact with system 10. In one example, user interface 16is implemented as a touchscreen having a screen that a user canphysically touch to communicate with system 10.

In the illustrated example, user interface 16 is shown as a display ortouch screen mounted on a pole extending vertically from cabinetstructure 12. When so configured, user interface 16 may be rotatablycoupled to the mounting pole so as to be swiveled to any rotationalposition desired by a user and/or translated to different verticalpositions. While user interface 16 is illustrated as being physicallyattached to cabinet structure 12, in other applications, user interface16 may be physically separated from the cabinet structure. For example,user interface 16 may be provided through a mobile communication device(e.g., smart phone, tablet computer) or otherwise physically separatefrom cabinet structure 12 and communicatively coupled to componentscontained therein.

System 10 can include a variety of other features and functionalities.FIG. 3 is a rear view of system 10 shown in FIGS. 1 and 2 illustratingadditional example features that can be included on the system. In thisexample, system 10 includes a handle 22 extending outwardly from cabinetstructure 12 to provide a surface that an operator can grasp to move thesystem from one location to another location. System 10 also includes apower connection 24. In different examples, system 10 may be powered viaa wired connection to wall or mains power, via a rechargeable battery,or through a combination of power sources. Power connection 24 may be asocket to which an electrical cable can be connected or may be anelectrical cable, for example that is retractable inside of cabinetstructure 12, to enable connection to an external power source. Powerdelivered to system 10 via power connection 24 may be used to directlypower the various electrical components of the system, such as acontroller and/or pump, or may provide power to a battery containedwithin cabinet structure 12 that then powers the various components ofthe system.

In some examples, system 10 may also include a printer 26 that canprovide printed summaries, reports, or other printed media relating tosystem 10. For example, printer 26 may be used to generate patientreports containing data related to a specific patient infusion procedureundertaken. The patient report may be incorporated into a patient'sfile, shared with the caregiver, or otherwise used to document caredelivered using the infusion system. As another example, printer 26 maybe used to generate maintenance reports indicating the status of one ormore components within system 10, document maintenance undertaken on thesystem, or otherwise record action taken on the system. Printer 26 canbe communicatively coupled to a controller that controls the overalloperation of system 10. In some examples, an operator may interact withthe user interface 16 to request one or more reports or other printedoutputs be generated using printer 26.

Although handle 22, power connection 24, and printer 26 are illustratedas being positioned on the rear side of cabinet structure 12 in theconfiguration of FIG. 3 , it should be appreciated that the features maybe positioned at other locations on system 10 while still providing thefunctionality described herein.

As briefly discussed above, system 10 may include a shielding assemblythat blocks radioactive radiation emitted by radioactive materialswithin the system. FIGS. 4 and 5 are perspective and top views,respectively, of system 10 from FIGS. 1-3 shown with cabinet structure12 removed for purposes of illustration and illustrating an exampleshielding assembly arrangement. As shown in this example, system 10includes a shielding assembly 28 carried by a frame 30. In particular,in the illustrated configuration, shielding assembly 28 is mounted to ashielding assembly frame 32 which, in turn, is mounted to a cart frame30.

In general, frame 30 may be any rigid structure that defines a surfaceconfigured (e.g., sized and/or shaped) to receive and hold shieldingassembly 28. Frame 30 may have one or more horizontally oriented members34 on which a bottom surface of shielding assembly 28 rests when theshielding assembly is inserted onto the frame. In some examples, frame30 also includes one or more vertically extending members that extendalong sidewalls of shielding assembly 28, when the shielding assembly isinstalled in the frame. For example, as illustrated in the configurationof FIG. 4 , shielding assembly 28 includes a first vertical wall surface36A, a second vertical wall surface 36B, and a rear vertical wallsurface 36C that collectively define an opening configured to receiveand surround around at least a portion of shielding assembly 28.Configuring system 10 with frame 30 can be useful to provide a structurethat supports shielding assembly 28 and/or helps protect the shieldingassembly from damage or inadvertent physical contact. In the illustratedconfiguration, wheels 14 are operatively (e.g., mechanically) connectedto frame 30 and, more particularly, horizontally oriented member 34 ofthe frame. In other examples as indicated above, system 10 does notinclude wheels 14.

In some examples, a pump that pumps liquid through system 10 is carriedby frame 30 inside of cabinet structure 12 (in examples in which system10 includes an additional exterior cabinet structure). For example, withreference to FIG. 5 , frame 30 defines a space 38 offset from shieldingassembly 28 that is configured to receive a pump 40. In particular, withthe illustrated example, space 38 is positioned between a secondvertical wall surface 36B of frame 30 and shielding assembly 28, whenthe shielding assembly is installed on the frame. Space 38 can beconfigured (e.g., sized and/or shaped) to receive pump 40 and/or othercomponents of system 10 such as a controller, one or more servomotors tocontrol valves, or other operational hardware to enable system 10 toprovide the functions described herein. Such an arrangement may beuseful to co-locate hardware components of system 10 not in directcontact with radioactive materials with other components contained inshielding assembly 28 that are in direct contact with radioactiveemissions emitted by radioactive liquid generated using the system.

In FIGS. 4 and 5 , shielding assembly 28 is mounted to shieldingassembly frame 32 which, in turn, can be installed on frame 30 thatdefines a mobile cart frame. For example, shielding assembly 28 may bephysically and/or mechanically connected to shielding assembly frame 32,such that the shielding assembly is in direct physical contact with theshielding assembly frame. In turn, shielding assembly frame 32 can bereceived in a space defined by horizontally oriented member 34 andvertically oriented sidewalls 36A-C, e.g., such that the shieldingassembly frame 32 is in physical contact with frame 30. Shieldingassembly frame 32, similar to frame 30, maybe a rigid structure thatsurrounds and or encloses at least a portion of the sidewalls ofshielding assembly 28. For example, shielding assembly frame 32 mayprovide mechanical rigidity and/or support for shielding assembly 28 toallow the shielding assembly to be transported outside of system 10.

To enable efficient installation of shielding assembly 28 onto frame 30,shielding assembly frame 32 may include multiple hooks 42 positionedabout a perimeter of the shielding assembly that can be engaged by alifting device to lift shielding assembly frame 32, and the shieldingassembly carried 28 thereon, for installation onto cart frame 30. Duringassembly or maintenance, an operator may attach a lifting mechanism suchas a crane or block and tackle to hooks 42 to enable shielding assembly28 to be lifted and installed on cart frame 30. Pump 40 and othercomponents of system 10 carried by frame 30 outside of shieldingassembly 28 may or may not also be physically attached to shieldingassembly frame 32. In some examples, shielding assembly frame 32 carriesonly shielding assembly 28 and does not carry other components that arereceived on frame 30 adjacent to shielding assembly 28, such as pump 40,a controller controlling the operation of system 10, and other relatedhardware or software.

When system 10 includes frame 30 and/or shielding assembly frame 32,each frame may typically be made of a rigid material such as a rigidmetal or plastic that provide structural integrity to the overallsystem. While FIGS. 4 and 5 illustrate one example arrangement ofrespective frames that can receive various hardware components of system10, it should be appreciated that in other configurations, system 10does not include a separate shielding assembly frame and cart frame, ormay have a different configuration or arrangement of frame members thanthat illustrated.

Shielding assembly 28 and frame 30 can receive and hold variouscomponents of system 10 that enable the system to perform the functionsattributed to it herein. For example, as briefly indicated above, system10 may include a radioisotope generator that generates radioactiveeluate via an elution with an eluant. The system may include aradioisotope generator that contains radioactive material in order togenerate the radioactive eluate via elution. The system may also includemultiple detectors, such as a beta detector and a gamma detector,positioned downstream of the radioisotope generator to measureradioactive emissions emitted by radioactive eluate produced using thegenerator.

FIG. 6 is a block diagram illustrating an example arrangement ofcomponents that can included in system 10 to generate radioactive eluateand detect radioactive emissions. In the example, system 10 includes aneluant reservoir 50, previously-described pump 40, a radioisotopegenerator 52, a waste container 54, an eluate-receiving container 56, abeta detector 58, and a gamma detector 60. One or more fluid tubinglines can connect the various components of system 10 together.

For example, in the configuration of FIG. 6 , pump 40 receives eluantfrom eluant reservoir 50, pressurizes the eluant, and dischargespressurized eluant into an eluant line 62. A first diverter valve 64controls the flow of eluant to one of a radioisotope generator inletline 66 and a radioisotope generator bypass line 68. Eluant flowingthrough radioisotope generator bypass line 68 bypasses radioisotopegenerator 52 and can flow directly into an infusion tubing line 70.Infusion tubing line 70 can be in fluid communication with eithereluate-receiving container 56 (e.g., during a quality control procedure)or a patient catheter 72 (e.g., during a patient infusion procedure). Asecond multi-way valve 74 controls a flow of eluate generated by elutionwithin radioisotope generator 52 and received from a radioisotopegenerator discharge line 75 to either the infusion tubing line 70 or awaste line 76. Waste line 76 can be connected to waste container 54.

During operation, radioisotope generator 52 can generate radioactiveeluate via elution. For example, radioisotope generator 52 may be astrontium-rubidium generator containing Sr-82 bound on a supportmaterial, such as stannic oxide or tin oxide. Rb-82 is a daughter decayproduct of Sr-82 and binds less strongly to the support material thanthe strontium. As pressurized eluant from eluant reservoir 50 is passedthrough the radioisotope generator, the eluant may release Rb-82 so asto generate a radioactive eluate. For example, when the eluant is asaline (NaCl) solution, sodium ions in the saline can displace Rb-82 inthe generator so as to elute a Rb-82 chloride solution.

In other examples, radioisotope generator 52 can generate differenttypes of decay products besides Rb-82. The type of daughter decayproduct produced by radioisotope generator 52 can be controlled byselecting the type of radioisotope loaded onto the generator supportmaterial. Example types of radioisotope generators that can be used asradioisotope generator 52 include, but are not limited to, ⁹⁹Mo/^(99m)Tc(parent molybdenum-99 bound on a support material to produce daughterdecay product technetium-99m); ⁹⁰Sr/⁹⁰Y (parent strontium-90 bound on asupport material to produce daughter decay product yttrium-90);¹⁸⁸W/¹⁸⁸Re (parent tungsten-188 bound on a support material to producedaughter decay product rhenium-188); and ⁶⁸Ge/⁶⁸Ga (parent germanium-68bound on a support material to produce daughter decay productgallium-68). Yet other types of radioisotope generators that can be usedas radioisotope generator 52 include: ⁴²Ar/⁴²K; ⁴⁴Ti/⁴⁴Sc; ⁵²Fe/⁵²Mn;⁷²Se/⁷²As; ⁸³Rb/^(83m)Kr; ¹⁰³Pd/^(103m)Rh; ¹⁰⁹Cd/^(109m)Ag;¹¹³Sn/^(113m)In; ¹¹⁸Te/¹¹⁸Sn; ¹³²Te/¹³²I¹³⁷Cs/^(137m)Ba; ¹⁴⁰Ba/¹⁴⁰La;¹³⁴Ce/¹³⁴La; ¹⁴⁴Ce/¹⁴⁴Pr; ¹⁴⁰Nd/¹⁴⁰Pr; ¹⁶⁶Dy/¹⁶⁶Ho; ¹⁶⁷Tm/^(167m)Er;¹⁷²Hf/¹⁷²Lu; ¹⁷⁸W/¹⁷⁸Ta; ¹⁹¹Os/^(191m)Ir; ¹⁹⁴Os/¹⁹⁴Ir; ²²⁶Ra/²²²Rn; and²²⁵Ac/²¹³Bi.

To measure the radioactivity of one or more radioisotopes in theradioactive eluate generated via elution in system 10, the system mayinclude multiple detectors configured to receive and measure differentradioactive emissions produced by the radioactive eluate. For example,as shown in the example of FIG. 6 , system 10 may include a betadetector 58 and a gamma detector 60. Beta detector 58 can be positioneddownstream of radioisotope generator 52 to measure beta emissionsemitted by radioactive eluate produced by the generator. Gamma detector60 can also be positioned downstream of radioisotope generator 52 tomeasure gamma emissions emitted by the radioactive eluate produced bythe generator.

The specific locations of beta detector 58 and gamma detector 60 canvary. However, in the example of FIG. 6 , beta detector 58 is positionedbetween an outlet of radioisotope generator 52 and second multi-wayvalve 74, which is upstream of waste container 54 and infusion tubing 70along the fluid pathway from the radioisotope generator. By contrast,gamma detector 60 is positioned downstream of the outlet of theradioisotope generator 52 and beta detector 58. For example, gammadetector 60 may be positioned downstream of the second multi-way valve74 along the fluid pathway of infusion tubing 70.

In operation, beta detector 58 can measure beta emissions emitted byradioactive eluate generated by and discharged from radioisotopegenerator 52. In some examples, beta detector 58 is positioned in closeproximity to radioisotope generator discharge line 75 such that the betadetector can detect beta emissions emitted from radioactive eluatepresent in the discharge line. The radioactive eluate may be flowingthrough the radioisotope generator discharge line 75 toward infusiontubing 70 and/or waste line 76. Alternatively, the radioactive eluatemay be supplied to the radioisotope generator discharge line 75 and heldstatic (non-flowing) while the beta detector 58 measures beta emissionsemitted from the radioactive eluate. In yet other configurations, aneluate-receiving reservoir may be provided in fluid communication withradioisotope generator discharge line 75, for example via an additionalmulti-way valve, and beta detector 58 positioned to measure betaemissions from the radioactive eluate supplied to the eluate-receivingreservoir. In any configuration, beta detector 58 may measure betaemissions from radioactive eluate generated by the generator in order todetect and/or quantify one or more radioisotopes present in theradioactive eluate.

System 10 also includes a gamma detector 60. In operation, gammadetector 60 can measure gamma emissions emitted by radioactive eluategenerated by and discharged from radioisotope generator 52. For example,radioactive eluate generated by radioisotope generator 52 may bedischarged through radioisotope generator discharge line 75, divertervalve 74, infusion tubing 70, and supplied to eluate-receiving container56. Gamma detector 60 may be positioned in close proximity toeluate-receiving container 56 in order to detect gamma emissions emittedby the portion of radioactive eluate delivered to the receivingcontainer. For example, a clinician may attach an outlet of infusiontubing 70 to an inlet of eluate-receiving container 56 in order tosupply radioactive eluate to the receiving container. Upon subsequentlycontrolling pump 40 to generate radioactive eluate that is supplied tothe eluate-receiving container 56, gamma detector 60 may measure gammaemissions emitted by the radioactive eluate.

While FIG. 6 illustrates one example location for gamma detector 60,other locations may be used. For example, gamma detector 60 may bepositioned in close proximity to a tubing line downstream ofradioisotope generator 52, such as radioisotope generator discharge line75 and/or infusion tubing 70. In these examples, gamma detector maymeasure gamma emissions emitted by radioactive eluate flowing throughthe tubing line or a static (non-flowing) portion of radioactive eluateheld within the tubing line. Independent of the specific location of thegamma detector with in system 10, gamma detector 60 may measure gammaemissions from radioactive eluate generated by the radioisotopegenerator 52 in order to detect and/or quantify one or moreradioisotopes present in the radioactive eluate.

For example, gamma emissions measured by gamma detector 60 may be usedto detect and/or quantify one or more contaminating radioisotopes inradioactive eluate generated by radioisotope generator 52, while betaemissions measured by beta detector 58 may be used to detect and/orquantify one or more radioisotopes in the radioactive eluate targetedfor patient infusion. In some examples, beta detector 58 measures betaemissions from radioactive eluate flowing through radioisotope generatordischarge line 75 toward eluate-receiving container 56. Once theradioactive eluate has passed beta detector 58 and filledeluate-receiving container 56, either partially or fully, gamma detector60 may measure gamma emissions from that portion of radioactive eluatesupplied to the receiving container. In these applications, gammadetector 60 may measure gamma emissions from a portion of radioactiveeluate also emitting beta emissions which were detected by beta detector58 as the radioactive eluate flowed towards the eluate-receivingcontainer 56. In other operational configurations, beta detector 58 andgamma detector 60 may not measure radioactive emissions from the sameportion or volume of radioactive eluate but may measure radioactiveemissions from different portions of radioactive eluate.

Radioisotope generator system 10 in the example of FIG. 6 also includesa controller 80. Controller 80 may be communicatively coupled (e.g., viaa wired or wireless connection) to the various pump(s), valves, andother components of system 10, including beta detector 58 and gammadetector 60, so as to send and receive electronic control signals andinformation between controller 80 and the communicatively coupledcomponents. For example, controller 80 may receive data generated bybeta detector 58 indicative of the magnitude of beta emissions detectedby the detector. Controller 80 may further receive data generated bygamma detector 60 indicative of the amount and type (e.g., spectraldistribution) of gamma emissions detected by the detector. Controller 80may further process the data to determine an activity of differentisotopes in the eluate from which beta detector 58 and gamma detector 60detected beta emissions and gamma emissions, respectively. Controller 80may also manage the overall operation of radioisotope generator system10, including initiating and controlling patient dosing procedures,controlling the various valves and pump(s) in the system, receiving andprocessing signals from beta detector 58 and gamma detector 60, and thelike.

In operation, beta detector 58 can detect beta emissions emanating fromradioactive eluate positioned in front of the detector. Beta detector 58can include a variety of components to detect and process beta emissionsignals. In some configurations, beta detector 58 is implemented using asolid-state detector element such as a PIN photodiode. In theseconfigurations, the solid-state detector element can directly convertimpinging radioactive energy into electrons in the semiconductormaterial of the detector. The electrons can then be amplified into ausable signal (e.g., received by controller 80). In some examples, betadetector 58 includes a scintillator, which converts impingingradioactive energy into light pulses, which is then captured by anattached photon-to-electron converter such as a photomultiplier tube oravalanche photodiode. The choice of the scintillator can determine thesensitivity and the countrate performance. For example, beta detector 58may be implemented using a plastic scintillator when high sensitivityand high countrate performance are desired.

During operation, gamma detector 60 can detect gamma ray emissionsemanating from a portion of eluate positioned in close proximity to thedetector, e.g., statically positioned in eluate-receiving container 56.Gamma detector 60 may include a variety of different components todetect and process gamma ray radiation signals, such as a pulse sorter(e.g., multichannel analyzer), amplifiers, rate meters, peak positionstabilizers, and the like. In one example, gamma detector comprises ascintillation detector. In another example, gamma detector comprises asolid-state semiconductor detector.

The specific type of gamma detector selected for detector 60 can varybased on a variety of factors such as, e.g., the required resolution ofthe detector, the physical requirements for practically implementing thedetector in a system (e.g., cooling requirements), the expectedsophistication of the personnel operating the detector, and the like. Insome applications, gamma detector 60 is a scintillator-type detector,such as a comparatively low-resolution alkali halide (e.g., NaI, CsI) orbismuth germanate (e.g., Bi4Ge3O12, or BGO). In other applications,gamma detector 60 incorporates a higher-Z metallic species. An exampleis lutetium oxyorthosilicate, Lu2(SiO4)O(Ce) or LSO, which, thoughslightly better in resolution than BGO, may have limited applicabilitybecause of its relatively high intrinsic radiation. As another example,gamma detector 60 may be a cerium-doped lanthanum, such as LaCl3(Ce) orLaBr3(Ce).

In other applications, gamma detector 60 is a solid-statesemiconductor-type detector, such as a planar germanium detector. Forinstance, as another example, gamma detector 60 may be a solid-statesemiconductor-type telluride detector, such as cadmium-telluride orcadmium-zinc-telluride semiconductor detector. Gamma detector 60 may beoperated at room (ambient) temperature or may be cooled below roomtemperature (e.g., by a cooling device incorporated into radioisotopegenerator system 10) to increase the resolution of detector.

Gamma detector 60 can generate gamma ray spectroscopy data. For example,the detector may include a passive material that waits for a gammainteraction to occur in the detector volume. Example interactions may bephotoelectric effects, Compton effects, and pair production. When agamma ray undergoes a Compton interaction or pair production, forinstance, a portion of the energy may escape from the detector volumewithout being absorbed so that the background rate in the spectrum isincreased by one count. This count may appear in a channel below thechannel that corresponds to the full energy of the gamma ray.

A voltage pulse produced by gamma detector 60 can be shaped by amultichannel analyzer associated with the detector. The multichannelanalyzer may take a small voltage signal produced by the detector,reshape it into a Gaussian or trapezoidal shape, and convert the signalinto a digital signal. The number of channels provided by themultichannel analyzer can vary but, in some examples, is selected fromone of 512, 1024, 2048, 4096, 8192, or 16384 channels. The choice of thenumber of channels may depend on the resolution of the system, theenergy range being studied, and the processing capabilities of thesystem.

Data generated by gamma detector 60 in response to detecting gamma rayemissions may be in the form of a gamma ray spectrum that includespeaks. The peaks may correspond to different energy levels emitted bythe same or different isotopes within an eluate sample under analysis.These peaks can also be called lines by analogy to optical spectroscopy.The width of the peaks may be determined by the resolution of thedetector, with the horizontal position of a peak being the energy of agamma ray and the area of the peak being determined by the intensity ofthe gamma ray and/or the efficiency of the detector.

During operation (either a patient infusion procedure, a quality controlprocedure, a calibration procedure, or other operating procedure),controller 80 may receive data generated by beta detector 58 and/orgamma detector 60 indicative of beta emissions and gamma emissionsdetected by the respective detectors. Controller 80 may process the datato determine an activity of one or more radioisotopes in the radioactiveeluate from which beta detector 58 and/or gamma detector 60 detectedbeta emissions and/or gamma emissions, respectively. Controller 80 maymanage operation of system 10 based on the determined activity of theone or more radioisotopes.

For example, when radioisotope generator 52 is implemented using astrontium-rubidium radioisotope generator, controller 80 may receivedata from beta detector 58 indicative of beta emissions measured fromradioactive eluate flowing through radioisotope generator discharge line75. Controller 80 may not be able to resolve different radioisotopesfrom the beta emissions measured by beta detector 58 but may instead beprogrammed to assume that all such beta emissions are attributable toradioactive Rb-82 present in the radioactive eluate, since Rb-82 may beexpected to be the predominant radioactive species present. Accordingly,with reference to data stored in memory, controller 80 may determine anactivity of Rb-82 present in the radioactive eluate supplied fromradioisotope generator 52 based on a cumulative magnitude of betaemissions measured by beta detector 58.

Controller 80 may further receive in such examples data from gammadetector 60 indicative of gamma emissions measured from a portion ofradioactive eluate supplied to eluate-receiving container 56. Controller80 may determine which species of one or more other radioisotopes arepresent in the radioactive eluate and/or an activity level of thosespecies based on the received data from the gamma detector. For example,controller 80 may determine which species of radioisotopes and/or anactivity of those radioisotopes are present in the radioactive eluatebased on the amount and type (e.g., spectral distribution) of gammaemissions detected by gamma detector 60. For instance, controller 80 maydetermine an activity of Sr-82 and/or Sr-85 present in the radioactiveeluate, if any, which can be contaminants to the Rb-82 radioisotopeintended for patient infusion procedure.

Controller 80 may control operation of system 10 based on the measuredactivity of the radioisotope intended for patient infusion (for exampleRb-82) and/or based on the measured activity of one or moreradioisotopes species that are contaminants to such radioisotope (forexample, Sr-82 and/or Sr-85). Controller 80 may compare the activity ofone or more individual isotopes to one or more thresholds stored inmemory and control operation of system 10 based on the comparison.Controller 80 may take a variety of actions when a threshold isexceeded. As one example, controller 80 may initiate a user alert (e.g.,a visual, textual, mechanical (e.g., vibratory), audible user alert),e.g., by controlling user interface 16 to deliver the alert. As anotherexample, controller 80 may shut down pump 40 so as to cease generatingeluate. As yet another example, controller 80 may control secondmulti-way valve 74 to divert elute from infusion tubing 70 to waste line76.

As noted above, system 10 may include a waste container 54 and aneluate-receiving container 56. Waste container 54 and eluate-receivingcontainer 56 may each be structures configured to receive and holdliquid received from upstream tubing. In different examples, wastecontainer 54 and/or eluate-receiving container 56 may be reservoirspermanently formed in shielding assembly 28 (FIGS. 4 and 5 ) or may beremovable from the shielding assembly. For example, waste container 54and/or eluate-receiving container 56 may be a vessel (e.g., bottle,vial, canister, or other receptacle) configured to receive radioactiveeluate, each of which is removable from shielding assembly 28.

In general, waste container 54 is intended to receive radioactive eluateproduced upon activation of system 10, as pump 40 pumps eluant throughradioisotope generator 52 toward waste container 54. For example, inoperation, pump 40 may pump eluant through radioisotope generator 52while controller 80 controls second multi-way valve 74 to directradioactive eluate toward waste container 54. Upon determining that theradioactive eluate produced by radioisotope generator 52 has reached athreshold level of activity, controller 80 may control second multi-wayvalve 74 to direct the radioactive eluate to infusion tubing 70 (and topatient catheter 72 or eluate-receiving container 56 coupled thereto)instead of toward waste container 54. Controller 80 may determine thatthe radioactive eluate produced by radioisotope generator 52 has athreshold level of activity based on the beta emissions measured by betadetector 58, e.g., and threshold information stored in memory associatedwith the controller. In different examples, waste container 54 may besized to hold a volume of liquid received from radioisotope generator 52of at least 100 mL, such as at least 250 mL, or greater than or equal to500 mL. As one example, waste container 54 may be sized to hold from 250mL to 1 L.

In contrast to waste container 54 which is intended to receiveradioactive eluate produced by radioisotope generator 52 that isdesignated as waste, eluate-receiving container 56 can receivepatient-infusible radioactive eluate produced the radioisotopegenerator. Eluate-receiving container 56 may receive and hold a portionof the radioactive eluate produced by the radioisotope generator (e.g.,after controller 80 has actuated multi-way valve 74 to redirect theradioactive eluate being produced from waste line 76 to infusion tubing70). While eluate-receiving container 56 is being filled withradioactive eluate and/or after the eluate-receiving container hasfilled, gamma detector 60 may measure gamma emissions emanating from theradioactive eluate. In some examples, beta detector 58 measures betaemissions from radioactive eluate flowing through radioisotope generatordischarge line 75 as the eluate flows to eluate-receiving container 56,whereupon gamma detector 60 measures gamma omissions from that sameportion of eluate whose beta emissions were previously measured by thebeta detector.

Controller 80 may determine an activity of one or more radioisotopespresent in the radioactive eluate received by an eluate-receivingcontainer 56 based on the gamma emissions measured by gamma detector 60.If controller 80 determines that an activity of one or moreradioisotopes present in the radioactive eluate exceeds an allowablelimit (e.g., with reference to thresholds stored in a memory associatewith the controller) the controller may alert the user, for example viauser interface 16. Additionally or alternatively, controller 80 mayprevent a subsequent patient infusion procedure until it is determinedthat a radioisotope generator 52 (or replacement thereof) can produceradioactive eluate that does not contain one or more radioisotopes thatexceed allowable limit. In this way, gamma detector 60 may be positionedto evaluate the quality of radioactive eluate produced by radioisotopegenerator 52 and help ensure that the radioactive eluate produced by theradioisotope generator (e.g., eluate that will subsequently be producedduring one or more subsequent elutions of the generator) is safe forpatient infusion.

Although eluate-receiving container 56 can have a number of differentconfigurations, in some examples, the eluate-receiving container issized smaller than waste container 54. For example, eluate-receivingcontainer 56 may be sized to receive and hold a volume of liquid lessthan 500 mL, such as less than 250 mL or less than 100 mL. In oneexample, eluate-receiving container is sized to hold from 10 mL to 100mL. Further, while eluate-receiving container 56 can be implementedusing a variety of different types of containers, in some examples, theeluate-receiving container is fabricated of glass or plastic, such as aglass vial or bottle, or a plastic syringe or container. Such astructure may be useful in that the glass vial may limit the extent towhich gamma emissions are blocked or attenuated by the eluate-receivingcontainer, or may be more uniform, allowing gamma detector 60 toadequately detect gamma emissions emitted by the radioactive eluatedelivered to the container.

In practice, eluate-receiving container 56 may be reused for multiplequality control procedures or may be disposable after each qualitycontrol procedure. For instance, in some applications, an operator mayselect a new, previously unused, eluate-receiving container and insertthe container into an appropriate compartment of shielding assembly 28.After performing the quality control procedure, the operator can removethe eluate-receiving container, discard the contents of the containerappropriately, and then discard the container itself. Typically, wastecontainer 54 is a reusable structure, for example fabricated from metalglass or other compatible material, that may be removed and emptied fromshielding assembly 28 periodically but is not discarded after use.

As discussed above with respect to FIGS. 4 and 5 , system 10 may includea shielding assembly 28. Shielding assembly 28 can house variouscomponents of system 10 exposed to and/or in contact with radioactiveeluate. FIGS. 7A and 7B are perspective views of an exampleconfiguration of shielding assembly 28 from FIGS. 4 and 5 , shownremoved from cart frame 30 for purposes of illustration. FIG. 7Aillustrates shielding assembly 28 with doors attached, while FIG. 7Billustrates the shielding assembly with doors removed to show an examplearrangement of internal features.

In general, shielding assembly 28 may be formed of one or more materialsthat provide a barrier to radioactive radiation. The type of material ormaterials used to fabricate the shielding assembly and the thicknessesof those materials may vary, for example, depending on the type and sizeof radioisotope generator 52 used in the system and, correspondingly,the amount of radiation shielding needed. In general, the thicknessand/or configuration of the radiation shielding material used to formshielding assembly 28 may be effective to attenuate radiation emanatingfrom inside of the shielding assembly to a level which is safe foroperating personnel to work around system 10. For example, when a newstrontium-rubidium generator is installed in shielding assembly 28, itmay contain 200 millicuries of radiation. Shielding assembly 28 mayblock that radiation so the radiation level outside of the shieldingassembly does not exceed that which is allowable for operating personnelsurrounding the shielding assembly.

In some examples, shielding assembly 28 is fabricated from lead or leadalloys or other high density materials. Shielding assembly 28 may have awall thickness greater than 25 millimeters, such as greater than 50millimeters. For example, shielding assembly 28 may have a wallthickness ranging from 50 millimeters to 250 millimeters, such as from65 millimeters to 150 millimeters. Further, as discussed in greaterdetail below, shielding assembly 28 may include different compartmentsspecifically arranged relative to each other to effective shieldradiation sources from radiation sensitive components.

With reference to FIGS. 7A and 7B, shielding assembly 28 can have atleast one sidewall 100 that provides a barrier to radioactive radiationand defines a compartment configured to receive one or more componentsof system 10. In some examples, shielding assembly 28 defines only asingle compartment, e.g., containing at least radioisotope generator 52(FIG. 6 ). In other examples, including the example illustrated in FIGS.7A and 7B, shielding assembly 28 has a plurality of compartments eachseparated from each other by at least one wall of radiation shieldingmaterial. For example, shielding assembly 28 may include a firstcompartment 102 configured to receive radioisotope generator 52, asecond compartment 104 configured to receive beta detector 58, and athird compartment 106 configured to receive gamma detector 60. Shieldingassembly 28 can include one or more additional compartments, such as afourth compartment 108 configured to receive waste container 54 and/or asidewall compartment 110 configured to receive one or more fluid tubinglines.

In general, the different compartments of shielding assembly 28 may beconfigured to position the different components received in eachrespective compartment at a desired location relative to each other. Forexample, first compartment 102 that is configured to receiveradioisotope generator 52 may be positioned at a location upstream ofsecond compartment 104 and third compartment 106. As a result,radioactive eluate generated by radioisotope generator 52 can flowdownstream to beta detector 58 and/or gamma detector 60 in order tomeasure an activity of one or more radioactive species that may bepresent in the radioactive eluate. As another example, when gammadetector 60 is located downstream of beta detector 58, secondcompartment 104 that is configured to receive the beta detector can bepositioned at a location upstream of third compartment 106 that isconfigured to receive gamma detector 60.

Positioning radioisotope generator 52 relative to beta detector 58and/or gamma detector 60 via shielding assembly 28 can be useful to helpproperly shield the detectors from radioactive radiation emitted by thegenerator. As discussed above, radioisotope generator 52 can contain aradioactive material, for example strontium-82, which emits radioactiveradiation. Nuclear decay of the radioactive material contained inradioisotope generator 52 can produce a decay product, or isotope, thatis released into eluant pumped through the generator for injection intoa patient undergoing a diagnostic imaging procedure. Since radioisotopegenerator 52 provides the source of nuclear material for the entireradioisotope generator system, the magnitude of radioactive admissionsemitted by the generator, and more particularly radioactive materialcontained on and/or in the generator, may provide the strongestradioactive admissions signal in the system. As a result, ifradioisotope generator 52 is not properly shielded from beta detector 58and/or gamma detector 60, the detectors may be overwhelmed by detectionof radioactive emissions emitted from the generator itself as opposed toradioactive emissions from the radioactive eluate generated by thegenerator, which may be desirably measured. Accordingly, shieldingassembly 28 can be configured to help shield beta detector 58 and gammadetector 60 from radioisotope generator 52 while still allowingradioactive eluate produced by the generator to flow from onecompartment to another compartment, for example, to allow the betadetector and the gamma detector to detect emissions from the eluate.

In some examples, radioisotope generator 52, beta detector 58, and gammadetector 60 are each positioned in different planes both horizontallyand vertically. For example, shielding assembly 28 may be divided intoan infinite number of infinitesimally thick planes extending in the X-Ydirection indicated on FIGS. 7A and 7B and positioned at differentvertical elevations in the Z-direction indicated on the figures(horizontal planes). Similarly, shielding assembly 28 may be dividedinto an infinite number of infinitesimally thick planes extending in theZ-X direction indicated on FIGS. 7A and 7B and positioned at differentlocations along the length of the assembly in the Y-direction indicatedon the figures (vertical planes). Radioisotope generator 52, betadetector 58, and gamma detector 60 may be arranged relative to eachother so they are each in a different horizontal plane and/or adifferent vertical plane. When so arranged, there may be at least onehorizontal plane and/or at least one vertical plane that intersects arespective one of radioisotope generator 52, beta detector 58, and gammadetector 60 but does not intersect the other two components. Such anarrangement may help maximize a distance between radioisotope generator52 and beta detector 58 and/or gamma detector 60, for example, toincrease an amount of shielding present between the radioisotopegenerator and one or both detectors.

In some configurations, gamma detector 60 is positioned at a higherelevation (e.g., in the positive Z-direction indicated on FIGS. 7A and7B) than the elevation at which radioisotope generator 52 is positioned.Additionally or alternatively, gamma detector 60 may be positioned at alocation that is a laterally offset (e.g., in the X-direction and/orY-direction indicated on FIGS. 7A and 7B) relative to radioisotopegenerator 52. Offsetting gamma detector 60 relative to radioisotopegenerator 52 both vertically and laterally may be useful to helpmaximize an amount of shielding material present between the gammadetector and the radioisotope generator.

Each compartment of shielding assembly 28 may define a cavity thatpartially or fully surrounds a respective component received in thecompartment, e.g., to partially or fully surround the component withradioactive shielding material. In the example of FIGS. 7A and 7B, firstcompartment 102 is defined by a sidewall 102A and a base or bottom wall102B. The sidewall 102A may extend vertically upwardly (in the positiveZ-direction indicated on FIGS. 7A and 7B) from the base wall 102B anddefine an opening 102C (on FIG. 7B) through which radioisotope generator52 can be inserted.

Second compartment 104 may also include a sidewall 104A and a base orbottom wall 104B. The sidewall 104A may extend vertically upwardly (inthe positive Z-direction indicated on the figures) from the base wall104B to form a cavity bound collectively by the sidewall 104A and thebase wall 104B. In some examples, the sidewall 104A may also extendvertically downwardly (in the negative Z-direction indicated on thefigures) from the base wall 104B to form an additional cavity on thebottom side of the base wall bound by the sidewall 104A and, on the topside, by base wall 104B. Independent of whether sidewall 104A extendsvertically above and/or below base wall 104B, in configurations in whichsecond compartment 104 includes base wall 104B, an opening 112 may beformed through the base wall 104B. The opening may be a region extendingthrough the thickness of base wall 104B that is devoid of radiationshielding material. When so configured, beta detector 58 may bepositioned on one side of base wall 104B at opening 112 and/or extendingthrough the opening. For example, beta detector 58 may be positionedunder base wall 104B and surrounded by a portion of sidewall 104Aextending vertically downwardly from the base wall.

In instances in which beta detector 58 is positioned on one side of basewall 104B (e.g., on underside of the base wall as discussed above), atubing line can be positioned on the opposite side of the base wall. Forexample, a tubing line that is part of an infusion tubing circuit may bepositioned in second compartment 104, for example with the tubing linepositioned over opening 112. In the configuration of FIGS. 7A and 7B,sidewall 104A defines an opening 104C (on FIG. 7B) through which atubing line (e.g., which may be part of an infusion tubing circuit) canbe installed in the compartment. Installing the tubing line in thesecond compartment 104 can position the tubing line to extend overopening 112 and the beta detector 58 positioned under the opening and/orextending upwardly through the opening. As a result, when radioactiveeluate is supplied to and/or through the tubing line, the radioactiveeluate may be positioned in and/or pass through the portion of thetubing line extending over opening 112. Beta detector 58 can detect betaemissions emanating from the radioactive eluate in the portion of thetubing positioned over opening 112, for example, while passing throughbase wall 104B via the opening.

When the second compartment 104 is intended to receive an infusiontubing circuit that includes one or more tubing lines arranged asdiscussed with respect to FIG. 6 , the portion of the infusion tubingcircuit positioned in the compartment may include a portion ofradioisotope generator discharge line 75, a portion of waste line 76,second multi-way valve 74, and a portion of infusion tubing 70. Toenable second multi-way valve 74 to be operatively connected to acontrol device (e.g., motor) through shielding assembly 28, secondcompartment 104 may also include a second opening 114 (e.g., asillustrated on FIG. 7B) formed through the base wall 104B. The secondopening 114 may be sized and positioned to enable second multi-way valve74 to be operatively connected to a control device positioned outside ofthe shielding assembly. During use, an operator may install a portion ofan infusion tubing circuit through opening 104C into second compartment104 such that sidewall 104A and base wall 104B collectively bound theportion of the inserted infusion tubing circuit with the material thatprovides a barrier to radioactive radiation. The second multi-way valve74 can be operatively connected with the control device through secondopening 114, and a portion of the infusion tubing circuit, such asradioisotope generator discharge line 75, can be positioned to extendover opening 112 to enable beta detector 58 to detect beta emissionsthrough the opening and the portion of tubing positioned there over.

As noted above, shielding assembly 28 in the example of FIGS. 7A and 7Balso includes a third compartment 106. Third compartment 106 may bedefined by a sidewall 106A that forms an opening 106B. Third compartment106 can be configured (e.g., sized and/or shaped) to receive gammadetector 60. In addition, the third compartment 106 may be configured tobe placed in fluid communication with the infusion tubing 70, when theinfusion tubing is installed in shielding assembly 28. During operation,such as a quality control procedure, radioactive eluate generated byradioisotope generator 52 positioned in first compartment 102 can flowthrough one or more tubing lines of the infusion tubing circuit to gammadetector 60 in third compartment 106. Radioactive eluate so delivered tothe third compartment 106 can emit gamma emissions that can be detectedby the gamma detector 60 in the compartment.

In some examples, third compartment 106 is configured (e.g., sizedand/or shaped) to receive an eluate-receiving container through opening106B. For example, after gamma detector 60 is installed in thirdcompartment 106, the eluate-receiving container may be positioned in thecompartment adjacent to and/or over the gamma detector. Infusion tubingline 70 can then be placed in fluid communication with theeluate-receiving container such that, when eluant is pumped through theradioisotope generator, eluate generated by the generator can flowtowards the eluate-receiving container and partially or fully fill thecontainer. Once suitably filled, a static (non-flowing) portion ofradioactive eluate can be positioned in third compartment 106 along withgamma detector 60. The static portion of radioactive eluate can emitgamma emissions that can be detected by gamma detector 60, for exampleto determine an activity of one or more radioisotopes present in theradioactive eluate.

In some examples, including the example illustrated in FIGS. 7A and 7B,shielding assembly 28 includes one or more additional compartmentsbesides first compartment 102, second compartment 104, and thirdcompartment 106. For example, shielding assembly 28 may include fourthcompartment 108 that is configured to receive and hold a waste container(e.g., waste container 54 from FIG. 6 ). Fourth compartment 108 mayinclude a sidewall 108A and a base wall 108B. The sidewall 108A of thefourth compartment can extend vertically from the base wall 108B todefine an opening 108C through which waste container 54 can be insertedinto the compartment. The sidewall 108A and base wall 108B cancollectively bound a space configured to receive and hold the wastecontainer. When waste container 54 is installed in fourth compartment108, waste line 76 may be placed in fluid communication with the wastecontainer.

To enable the various tubing lines of the radioisotope generator systemto extend from one compartment to an adjacent compartment, shieldingassembly 28 may include additional tubing pathways and/or tubingcompartments to facilitate routing of the tubing lines. In the exampleof FIGS. 7A and 7B, shielding assembly 28 includes a sidewallcompartment 110. The sidewall compartment 110 in this example is definedby a recessed cavity formed in sidewall 108A of fourth compartment 108.In particular, in the illustrated arrangement, sidewall compartment 110extends vertically (in the Z-direction indicated on FIG. 7B) along theexterior surface of sidewall 108A defining the fourth compartment 108configured to receive waste container 54. Sidewall compartment 110 canbe configured to receive one or more portions of tubing, such as atleast a portion of infusion tubing 70 and at least a portion of wasteline 76.

When installed, waste line 76 may extend from second multi-way valve 74positioned over opening 114 in second compartment 104 through sidewallcompartment 110 to fourth compartment 108. Similarly, infusion tubing 70may extend from second multi-way valve 74 positioned over opening 114 insecond compartment 104 through sidewall compartment 110 and subsequentlyout of the sidewall compartment. In different configurations, infusiontubing 70 may or may not exit shielding assembly 28 before returning tothe shielding assembly by having an outlet of infusion tubing 70positioned in third compartment 106, for example in fluid communicationwith an eluate-receiving container positioned in the third compartment.

Shielding assembly 28 may include additional tubing pathways formed inor through one or more sidewalls to find the compartments of theassembly in order to facilitate routing of tubing between adjacentcompartments. For example, the sidewall 104A defining second compartment104 may include an eluant tubing pathway 116 formed through thesidewall. As another example, the sidewall 102A defining firstcompartment 102 may include an eluate tubing pathway 118A and agenerator discharge tubing pathway (which may also be referred to as aneluate tubing pathway) 118B. When so configured, eluant line 62 (FIG. 6) can enter shielding assembly 28 via eluant tubing pathway 116 andfurther extend from the second compartment 104 into the firstcompartment 102 via eluant tubing pathway 118A. Eluate line 62 can beconnected with pump 40 on one end (e.g., outside of shielding assembly28, in configurations where the pump is located outside of the shieldingassembly) and with radioisotope generator 52 in first compartment 102 onan opposite end. Radioactive eluate produced via the generator candischarge via radioisotope generator discharge line 75 and can flow outof first compartment 102 via radioisotope generator discharge line 75positioned in eluate tubing pathway 118B.

To secure eluant line 62 in eluant tubing pathway 118A and radioisotopegenerator discharge line 75 in eluate tubing pathway 118B, respectively,shielding assembly 28 may include a tube lock 120. Tube lock 120 may bea structure which is movable over eluant tubing pathway 118A and eluatetubing pathway 118B to secure or lock each tube in a respective pathway.This can prevent one or more of the tubes from inadvertently coming outof its respective pathway and being crushed when the door enclosingfirst compartment 102 or second compartment 104 is closed.

As briefly discussed above, when shielding assembly 28 is configuredwith multiple compartments, the compartments may be arranged relative toeach other to help shield beta detector 58 and/or gamma detector 60 fromradioactive emissions emanating from radioisotope generator 52 itself.This can allow one or both detectors to detect radioactive emissionsassociated with radioactive eluate generated by the generator ratherthan radioactive emissions associated with the generator itself. Inapplications where the radioisotope generator system includes both abeta detector and a gamma detector, the gamma detector may be moresensitive to background radiation from the radioisotope generator thanthe beta detector. That is, the gamma detector may be more prone tobeing saturated by being exposed to gamma emissions emanating from theradioisotope generator itself than the beta detector. For these andother reasons, the gamma detector may be positioned in such a wayrelative to the radioisotope generator so as to try and minimizeexposure to gamma radiation from the radioisotope generator, forexample, by maximizing an amount of shielding material positionedbetween the gamma detector and radioisotope generator.

In general, the amount of shielding material positioned between gammadetector 60 and radioisotope generator 52 may be increased bypositioning one or more compartments of shielding assembly 28 betweenfirst compartment 102 and third compartment 106 rather than positioningthe compartments directly adjacent to each other. In some examples,shielding assembly 28 is configured so that at least one compartment ispositioned between first compartment 102 and third compartment 106(e.g., along the length of the shielding assembly in the Y-directionindicated on FIGS. 7A and 7B and/or vertically in the Z-directionindicated on the figures). For example, second compartment 104 may bepositioned between first compartment 102 that is configured to receiveradioisotope generator 52 and third compartment 106 that is configuredto house gamma detector 60. As a result, the sidewall 102A definingfirst compartment 102, the sidewall 104A defining the second compartment104, and the sidewall 106A defining the third compartment, in each caseformed of material that provides a barrier to radioactive radiation, canbe located between the radioisotope generator 52 and gamma detector 60,when installed in shielding assembly 28. Thus, the amount of shieldingmaterial present between radioisotope generator 52 and gamma detector 60may be the combined thicknesses of the sidewalls.

In configurations where shielding assembly 28 includes more than threecompartments, such as illustrated in the example of FIGS. 7A and 7B, oneor more of the other compartments may also be positioned between firstcompartment 102 and third compartment 106. In the illustrated example,fourth compartment 108 is also positioned between the first compartment102 and third compartment 106. In this arrangement, both secondcompartment 104 and fourth compartment 108 (as well as sidewallcompartment 110) are located between first compartment 102 and thirdcompartment 106. As a result, the sidewall 102A defining firstcompartment 102, the sidewall 104A defining the second compartment 104,the sidewall 108A defining the fourth compartment 108, and the sidewall106A defining the third compartment, in each case formed of materialthat provides a barrier to radioactive radiation, can be located betweenthe radioisotope generator 52 and gamma detector 60, when installed inshielding assembly 28. Again, the amount of shielding material presentbetween radioisotope generator 52 and gamma detector 60 may be thecombined thicknesses of the sidewalls, providing increased shieldingprotection as opposed to if fewer sidewalls or a lesser thickness ofsidewall material was located between the components.

Independent of whether shielding assembly 28 includes one or morecompartments between first compartment 102 and third compartment 106,offsetting the location of gamma detector 60 in third compartment 106relative to the location of radioisotope generator 52 in firstcompartment 102 (e.g., horizontally and/or vertically) may be useful toincrease the amount of shielding material present between the gammadetector and radioisotope generator. Offsetting the two componentsrelative to each other in three-dimensional space can increase theamount of shielding material positioned between the components, therebyincreasing the amount of radiation blocked by the shielding material.

In practice, a radiation path may be defined from radioisotope generator52 to gamma detector 60 when the components are installed in shieldingassembly 28. The radiation path may be a linear path or route taken bythat portion of the radioactive emissions (e.g., beta particles and/orgamma rays) emitted by the radioisotope generator that travel to thegamma detector (e.g., can be detected by the gamma detector if nototherwise blocked). The radiation path may be the shortest lineardistance between radioisotope generator 52 and gamma detector 60 (e.g.,the active surface of the gamma detector that detectors gamma rays).Depending on the configuration of the radioisotope generator system, theshortest linear distance may be from the top of radioisotope generator52 to the top of gamma detector 60, which is configured to detectradioactive emissions emanating from radioactive eluate received in thethird compartment 106.

The shielding material forming the one or more sidewalls 100 ofshielding assembly 28 can block radiation along the radiation path fromthe radioisotope generator to the gamma detector, for example to preventgamma detector 60 from detecting background radiation from radioisotopegenerator 52 above a desired level. This can be useful to help ensurethat gamma detector 60 accurately measures the radioactivity ofradioactive eluate generated by the generator and conveyed to thirdcompartment 106 and does not erroneously measure radioactive activeemissions emitted by the generator itself as being as being attributableto the radioactive eluate.

FIG. 7C is a perspective view of shielding assembly 28 from FIGS. 7A and7B shown sectionalized along the A-A sectional line indicated on FIG.7A, while FIG. 7D is a side view of shielding assembly 28 from FIGS. 7Aand 7B shown sectionalized along the B-B sectional line indicated onFIG. 7A. FIG. 7D illustrates shielding assembly 28 without doorsattached for purposes of illustration. As shown in this example, aradiation path 130 is defined from radioisotope generator 52 in firstcompartment 102 to gamma detector 60 in third compartment 106. Radiationpath 130 passes through at least a portion of the first compartment 102(e.g., sidewall 102A of the compartment) and at least a portion of thirdcompartment 106 (e.g., sidewall 106A of the compartment). When shieldingassembly 28 includes one or more other compartments positioned betweenfirst compartment 102 and third compartment 106, radiation path 130 mayor may not also pass through portions of those one or more othercompartments.

For example, in the illustrated configuration, radiation path 130 passesthrough first compartment 102, second compartment 104, and fourthcompartment 108, before passing into the third compartment 106.Depending on the arrangement of the different compartments, radiationpath 130 may pass through a side wall and/or base wall defining eachcompartment. In the example of FIGS. 7C and 7D, radiation path 130extends from radioisotope generator 52 in first compartment 102 throughsidewall 102A, through sidewall 104A which is shared and coextensivewith sidewall 102A, through sidewall 108A, and finally through sidewall106A before reaching the active surface of gamma detector 60 thatdetects gamma emissions. In effect, radiation path 130 defines an axisextending from and/or through radioisotope generator 52 and gammadetector 60 that transects (e.g., cuts across) the second compartment104 and fourth compartment 108 between first compartment 102 and thirdcompartment 106. Because gamma radiation emitted from radioisotopegenerator 52 needs to travel through each of these surfaces that providea barrier to radioactive radiation before reaching gamma detector 60,the amount of gamma radiation reaching the detector is reduced ascompared to if less shielding material were provided between theradioisotope generator and the gamma detector. In turn, this reduces theamount of background radiation, or amount of ambient radiation, thatgamma detector 60 may detect even when radioactive eluate is notsupplied to third compartment 106.

In some examples, third compartment 106 and/or gamma detector 60 locatedin the compartment is positioned at a different elevation with respectto ground than first compartment 102 and/or radioisotope generator 52positioned in the compartment. This may increase the amount of shieldingmaterial positioned along radiation path 130, for example, by extendingthe length of the path as opposed to if the gamma detector 60 is at thesame elevation as radioisotope generator 52. By positioning thirdcompartment 106 and/or gamma detector 60 at a different elevationrelative to first compartment 102 and/or radioisotope generator 52, thelength of radiation path 130 can be increased without needing toincrease the overall footprint of the radioisotope generator system, asmay otherwise be needed to increase the length of the radiation pathwithout changing elevation.

In different examples, third compartment 106 and/or gamma detector 60may be located at a higher elevation or a lower elevation with respectto ground relative to first compartment 102 and/or radioisotopegenerator 52. In the illustrated example, third compartment 106 andgamma detector 60 contained therein are both positioned at a higherelevation with respect to ground than first compartment 102 andradioisotope generator 52 contained therein. Positioning thirdcompartment 106 at a higher elevation than the first compartment 102 maybe useful to provide an ergonomically efficient arrangement. Inpractice, radioisotope generator 52 may be a comparatively heavycomponent that is replaced on a comparatively infrequent basis.Positioning radioisotope generator 52 close to ground can be helpful sothe operator does not need to lift radioisotope generator 52 to a highheight when replacing it. By contrast, an eluate-receiving containerpositioned in third compartment 106 may be replaced on a comparativelyfrequent basis, such as once per day. Further, the eluate-receivingcontainer may be a comparatively light component that is easily lifted.Accordingly, positioning third compartment 106 at a higher elevationthan first compartment 102 can be helpful, for example so that anoperator does not need to bend over or bend over too far to replace theeluate-receiving container. In addition, positioning first compartment102 at a lower elevation than third compartment 106 may lower the centerof gravity of system 10, making the system more stable.

In some examples, radiation path 130 extends at a non-zero degree angle132 with respect to ground to position radioisotope generator 52 andgamma detector 60 at different elevations. While angle 132 may vary, insome examples, the angle ranges from 30° to 75° with respect to ground.In other examples, the angle ranges from 30° to 40°, from 40° to 45°,from 45° to 50°, from 50° to 60°, or from 60° to 75°. In one particularexample, the angle ranges from 43° to 47°. The angle may be positive ifgamma detector 60 is at a higher elevation than radioisotope generator52 or may be negative if gamma detector 60 is at a lower elevation theradioisotope generator 52.

When the third compartment 106 is positioned at a higher elevation withrespect to ground than first compartment 102, the top surface of theopening 106C of the third compartment (e.g., rim of the compartment) maybe higher than the top surface of the opening 102C of the firstcompartment (e.g., rim of the compartment). In some examples, theopening of the third compartment is at least 10 centimeters higher thanthe opening of the first compartment, such as at least 25 centimetershigher or at least 30 centimeters higher. For example, the opening ofthe third compartment may range from 10 centimeters to 100 centimetershigher than the opening of the first compartment, such as from 20centimeters to 50 centimeters. Additionally or alternatively, theopening of the third compartment may be spaced horizontally (e.g., inthe X and/or Y-direction indicated on FIG. 7C) from the opening of thefirst compartment, for example to increase the separation distancebetween the compartments and the amount of shielding material positionedthere between. For example, the opening 106C of the third compartmentmay be spaced at least 20 centimeters from the opening of the firstcompartment, such as at least 35 centimeters. In some examples, theopening 106C of the third compartment is spaced from 20 centimeters to50 centimeters from the opening of the first compartment. In each case,the horizontal distance between the openings of the compartments can bemeasured from the center of one compartment to the center of the othercompartment.

Independent of the specific way in which first compartment 102 andradioisotope generator 52 contained therein are arranged relative tothird compartment 106 and gamma detector 60 contained therein, shieldingassembly 28 may provide a sufficient amount of radiation shieldingmaterial between the radioisotope generator and gamma detector. Theamount of shielding material present between radioisotope generator 52and gamma detector 60 may be effective to ensure that backgroundradiation in the third compartment caused by the radioisotope generatoris sufficiently low for the gamma detector to detect a desired level ofradiation emitted by radioactive eluate in the third compartment, forexample when the radioactive eluate is supplied to an eluate-receivingcontainer in the compartment. In some examples, the desired level ofradiation is less than 0.6 microcuries of Sr-82. For example, thedesired level of radiation may be less than 0.5 microcuries of Sr-82,less than 0.4 microcuries of Sr-82, less than 0.3 microcuries of Sr-82,less than 0.2 microcuries of Sr-82, or less than 0.1 microcuries ofSr-82. In yet other applications, the desired level of radiation is lessthan 0.05 microcuries of Sr-82, less than 0.02 microcuries of Sr-82, orless than 0.01 microcuries of Sr-82. Since the activity of radioactiveeluate in the eluate-receiving container (e.g., after decay of aninitially-present short-lived radioisotope such as Rb-82) may beexpected to be less than this level of radiation, gamma detector 60 maybeneficially detect radiation levels below this level withoutinterference of background radiation. While the total amount ofradiation shielding material positioned along radiation path 130 mayvary, in some examples, shielding assembly 28 has at least 20centimeters of shielding material positioned on the pathway (e.g., suchthat the radiation path needs to travel through this length of materialbefore reaching gamma detector 60), such as at least 30 centimeters ofshielding material. For example, shielding assembly 28 may be configuredto provide from 20 centimeters to 50 centimeters of shielding materialon the pathway, such as from 30 centimeters to 40 centimeters ofshielding material.

To increase the amount of shielding material located along radiationpath 130, the compartments may be arranged so the radiation path crossespreferentially through sidewalls defining the compartments rather thanthe void space of the compartments themselves. That is, instead ofconfiguring the compartments so that radiation path 130 passespreferentially through the open areas of the compartments, thecompartments may be arranged relative to each other so that theradiation path passes through sidewall sections of the compartments.

FIG. 7E is a top view of shielding assembly 28 from FIGS. 7A and 7B(shown with doors removed) illustrating an example arrangement ofcompartments in which radiation path 130 passes through one or moresidewall sections defining the compartments. For example, in theillustrated configuration, fourth compartment 108 is a laterally offset(in the X-direction indicated on FIG. 7E) from radiation path 130 suchthat the radiation path travels through sidewall 108A instead of thevoid space in the center of the compartment. This can help maximizeradiation shielding provided by the fourth compartment, as compared toif the fourth compartment 108 is centered about it the radiation path.Since radiation path 130 may be dictated by the position of a gammadetector 60 and radioisotope generator 52, fourth compartment 108 can belaterally offset from the radiation path by controlling the position ofthird compartment 106 (which contains gamma detector 60) and firstcompartment 102 (which contains radioisotope generator 52) relative tothe fourth compartment.

In some examples, third compartment 106 is arranged relative to fourthcompartment 108 such that an axis 134 bisecting fourth compartment 108(e.g., that is parallel to the length of shielding assembly 28 in theY-direction indicated on FIG. 7E) is offset from an axis 136 bisectingthird compartment 106 (e.g., that is also parallel to the length ofshielding assembly 28). Each axis may bisect a respective compartment bydividing the compartment into two equally sized halves. The axis 136bisecting third compartment 106 may be offset relative to the fourthcompartment 108 such that the axis is co-linear with a section ofsidewall 108A of the fourth compartment. In the illustratedconfiguration, fourth compartment 108 includes a section of sidewall 138that is arcuate shaped and a section of sidewall 140 that is planar orlinear. The arcuate section of sidewall 138 and the linear section ofsidewall 140 may be contiguous with each other and, in combination, formsidewall 108A. With this arrangement, the linear section of sidewall 140is coaxial with axis 136 that bisects third compartment 106. As aresult, radiation emissions traveling along radiation path 130 in theillustrated configuration must travel through substantially the entirelength of the linear section of sidewall 140 before reaching gammadetector 60, which may increase the likelihood of the radiation beingblocked before reaching the gamma detector.

In some examples, the compartments of shielding assembly 28 are arrangedrelative to each other such that radiation path 130 travels through agreater length of shielding material than void space (e.g., for some orall of the compartments). For example, in FIG. 7E the compartments arearranged so that radiation path 130 travels through a length ofshielding material defining sidewall 108A (e.g., linear section ofsidewall 140) that is greater than a length the radiation path travelsthrough the void space or cavity formed by sidewall 108A. Asillustrated, radiation path 130 does not travel through any length ofvoid space defining fourth compartment 108. However, if thirdcompartment 106 were moved so that axis 136 is closer to axis 134, theradiation path may cross through a portion of the void space definingthe compartment. In this regard, while arranging third compartment 106and/or fourth compartment 108 relative to each other to align radiationpath 130 with one or more sidewall sections can be helpful to increasethe amount of radiation shielding, it should be appreciated that theshielding assembly in accordance with the disclosure is not limited tothis example arrangement of components. In other configurations, forexample, third compartment 106 and fourth compartment 108 may be alignedso that axis 134 is coaxial with axis 136.

In configurations where the third compartment 106 and fourth compartment108 are offset from each other, the axis 134 bisecting the fourthcompartment may be offset from the axis 136 bisecting the thirdcompartment by a distance 142. For example, the compartments may beoffset relative to each other by a distance of at least 2 centimeters,such as at least 4 centimeters, a distance ranging from 2 centimeters to10 centimeters, or a distance ranging from 4 centimeters to 6centimeters. When the third compartment 106 and fourth compartment 108are offset relative to each other, radiation path 130 may pass throughan offset side of the fourth compartment rather than directly throughthe center of the compartment. That is, radiation path 130 may notbisect the bisect the compartment which may cause the radiation path tocross the largest void space of the compartment but may instead beoffset preferentially to one side of the compartment or the other sideof the compartment relative to the bisecting axis. In some examples,fourth compartment is offset relative to radiation path 130 such thatthe radiation path passes through less than 10 centimeters devoid ofshielding material inside of the container, such as less than 5centimeters devoid of shielding material. Where radiation path 130crosses the void space of fourth compartment 108 between side wallsurfaces, the length of the chord formed between where the radiationpath intersects the two sidewall surfaces can be considered the lengththrough which the radiation path passes that is devoid of shieldingmaterial.

While the third compartment 106 and fourth compartment 108 can havedifferent positions and configurations as described herein, in theillustrated example of FIG. 7E, third compartment 106 is positionedlaterally offset of and directly adjacent to fourth compartment 108. Inthis example, third compartment 106 and fourth compartment 108 share anadjoining section of sidewall 144. In some examples, one or more (e.g.,all) of the compartments of shielding assembly 28 are formed isphysically separate structures that are then join together to form aunitary shielding assembly. For example, third compartment 106 andfourth compartment 108 may be fabricated (e.g., cast, machined, molded)as separate structures and then placed in direct contact with each otherto form shared sidewall 144. In other examples, one or more (e.g., all)of the compartments of shielding assembly 28 are formed together toprovide a permanent and physically joined structure. For example, thirdcompartment 106 and fourth compartment 108 may be fabricated together asa permanently joined structure.

While first compartment 102, third compartment 106, and fourthcompartment 108 are illustrated as defining a substantiallycircular-shaped compartment and second compartment 104 is illustrated asdefining a substantially rectangular-shaped compartment, thecompartments can define other shapes. In general, each compartment candefine any polygonal (e.g., square, hexagonal) or arcuate (e.g.,circular, elliptical) shape, or even combinations of polygonal andarcuate shapes. Accordingly, while each compartment of shieldingassembly 28 is described herein as being defined by a sidewall, itshould be appreciated that the sidewall may be a single contiguoussidewall or may have multiple individual sidewall sections which,collectively, define the sidewall. The specific shape of eachcompartment may vary based on the size and shape of the component ofcomponents intended to be inserted into the compartment.

With further reference to FIG. 7D, base wall 104B of second compartment104 may define a top surface 144A and a bottom surface 144B opposite thetop surface. When beta detector 58 is positioned below top surface 144A(and optionally below bottom surface 144B), second compartment 104 mayinclude an extension portion 146 extending downwardly from the base wall102B to protect beta detector 58 along its length. Extension portion 146can be configured (e.g., sized and/or shaped) to receive beta detector58. Extension portion 146 may have a height 148 (e.g., in theZ-direction indicated on FIG. 7D) greater than the length of betadetector 58. In some examples, extension portion 146 has a height 148greater than or equal to the height of first compartment 102, e.g., suchthat the extension portion extends downwardly to the same position orbelow that to which first compartment 102 extends.

To facilitate installation and removal of beta detector 58 as well aselectrical communication between the beta detector and a controller thatcontrols the infusion system (e.g., via wiring), an opening may beformed in extension portion 146. In some examples, the bottom end 150 ofextension portion 146 is open or devoid of material. When so configured,beta detector 58 may be inserted into and removed from the extensionportion via the open bottom end. Additionally, electrical communicationbetween beta detector 58 and a controller communicatively coupled to thebeta detector may be provided via one or more cables that extend fromthe controller to the beta detector through the open bottom and ofextension portion 146.

With continued reference to FIG. 7D, third compartment 106 may have aheight 152 (e.g., in the Z-direction indicated on FIG. 7D) greater thanthe length of beta detector 58. In some examples, third compartment 106has a height 152 greater than or equal to the height of fourthcompartment 108. In some examples, third compartment 106 extends from alocation that is coplanar with base wall 104B of second compartment 104vertically upwardly. For example, third compartment 106 may extendvertically upwardly to an elevation equal to or higher than the openingof fourth compartment 108. In other configurations, third compartment106 may extend below a location that is coplanar with base wall 104B.

Independent of the specific height of third compartment 106, thecompartment may have an opening to facilitate installation and removalof gamma detector 60. The opening may also provide access for electricalcommunication between the gamma detector and a controller that controlsthe infusion system (e.g., wiring). In some examples, the bottom and 154of third compartment 106 is open or devoid of material. When soconfigured, gamma detector 60 may be inserted into and removed fromthird compartment 106 via the open bottom end.

In other configurations, third compartment 106 may have an opening insidewall 106A through which gamma detector 60 can be inserted andremoved. In these configurations, third compartment 106 may include aside pocket or cavity to receive a gamma detector. In yet otherconfigurations, gamma detector 60 may be inserted through the open topend of third compartment 106 rather than through a separate access port.When gamma detector 60 includes open bottom and 154, however electricalcommunication between gamma detector 60 and a controller communicativelycoupled to the gamma detector may be provided via one or more cablesthat extend from the controller to the gamma detector through the openbottom and of third compartment 106.

The specific dimensions of the compartments of shielding assembly 28 mayvary, for example, based on the size and configuration of componentsused in the system. In some examples, the thickness of sidewall 102Aranges from 35 millimeters to 100 millimeters, the thickness of sidewall104A ranges from 80 millimeters to 140 millimeters, and the combinedthickness of sidewall 106A and sidewall 108A ranges from 125 millimetersto 175 millimeters. The foregoing dimensions are provided for purposesof illustration, and it should be appreciated that the shieldingassembly in accordance with the disclosure is not necessarily limited inthis respect.

To enclose the openings defined by the compartments of shieldingassembly 28, each compartment may have a corresponding door. Each doormay be opened by an operator to insert and/or remove components andclosed to provide an enclosed barrier to radioactive radiation andcomponents contained therein. Each door may be formed of the same or ofdifferent material used to form the least one sidewall 100 of shieldingassembly 28 and may provide a barrier to radioactive radiation. Withreference to FIG. 7A, each compartment of shielding assembly 28 isillustrated as including a door.

Specifically, in the illustrated configuration, first compartment 102 isenclosed by a door 102D, second compartment 104 is enclosed by a door104D, third compartment 106 is enclosed by a door 106D, fourthcompartment 108 is enclosed by a door 108D, and sidewall compartment 110is enclosed by a sidewall door 110D. Each door can be selectively openedto provide access to the respective compartment enclosed by the door.Each door can further be selectively closed to cover the openingproviding access to the respective compartment with radiation shieldingmaterial.

In the example of FIG. 7A, first compartment 102, second compartment104, third compartment 106, and fourth compartment 108 each define anopening that is oriented upwards with respect to gravity (e.g., definesan opening in the X-Y plane that can be accessed in the Z-directionindicated on the figure). In such an example, first door 102D seconddoor 104D, third door 106D, and fourth door 108D may each open upwardlywith respect to gravity to access a corresponding compartment enclosedby the door. This can allow an operator to insert and remove componentsfrom a respective one of the compartments by moving the door upwardly ordownwardly in the vertical direction. In other configurations, however,the opening defined by one or more of the compartments may not openupwardly with respect to gravity. For example, one or more (e.g., all)of the compartments may have a permanently enclosed top surface formedof radiation shielding material and may define an opening through asidewall forming the compartment. In these examples, a door used toprovide selective access to the opening formed in the sidewall may openlaterally rather than upwardly with respect to gravity. Other openingarrangements and door configurations for shielding assembly 28 can alsobe used in a shielding assembly in accordance with the disclosure, andthe disclosure is not necessarily limited in this respect.

In some examples, one or more of the doors of shielding assembly 28 mayinclude interlocks or overlapping door segments to prevent one or moreof the doors from inadvertently being opened. For example, one door mayhave a portion that overlaps an adjacent door, preventing the adjacentdoor from being opened before the door providing the overlapping portionis first opened. As one example arrangement, sidewall door 110D mayoverlap second door 104D which, in turn may overlap first door 102D. Asa result, second door 104D cannot be opened in such a configurationbefore sidewall door 110D is opened. Similarly, first door 102D cannotbe opened in such a configuration before second door 104D is opened. Insome configurations, fourth door 108D also overlaps sidewall door 110Dsuch that the sidewall door cannot be opened before the fourth door isopened. In general, arranging one or more doors to overlap with eachother can be useful to help prevent inadvertent opening of one or moreof the compartments of shielding assembly 28. For example, firstcompartment 102 may contain the greatest source of radioactive radiationwhen the radioisotope generator 52 is installed in the compartment. Forthis reason, shielding assembly 28 may be arranged so at least door 102Dis overlapped by adjacent door, helping to prevent an operator frominadvertently opening the compartment containing the largest source ofradiation.

The third compartment 106 containing the gamma detector 60 and/or aneluate-receiving container 56 may also include a door 106D. Door 106Dcan be opened to install eluate-receiving container 56 over gammadetector 60 and closed to enclose the eluate-receiving container in thecompartment for receiving radioactive eluate from the radioisotopegenerator. To place the eluate-receiving container positioned in thirdcompartment 106 in fluid communication with the radioisotope generator,an infusion tubing line may extend into the compartment and be in fluidcommunication with the eluate-receiving container. In some examples,sidewall 106A of the third compartment 106 has an opening or channelformed therein through which infusion tubing 70 passes to placeeluate-receiving container 56 in fluid communication with theradioisotope generator. In other examples, door 106D may include anopening through which infusion tubing 70 can pass and be coupled to theeluate-receiving container.

In the example of FIG. 7A, third door 106D includes an opening 158 thatis configured (e.g., sized and/or shaped) to receive infusion tubing 70.When assembled, infusion tubing 70 can extend out of shielding assembly28 (e.g., through an opening in the sidewall of the fourth compartment108 or sidewall compartment 110) and then reenter the shielding assemblythrough opening 158. A distal or terminal end of infusion tubing 70 mayproject into the third compartment 106 through opening 158 in door 106Dand be in fluid communication with eluate-receiving container 56contained therein.

Eluate-receiving container 56 can have a variety of differentconfigurations and be arranged in a number of different ways relative togamma detector 60 in third compartment 106. FIG. 7F is an exploded viewof a portion of shielding assembly 28 from FIG. 7D showing an examplearrangement of eluate-receiving container 56 to gamma detector 60. Asshown in this example, eluate-receiving container 56 is positioned inthird compartment 106 at a location that is vertically above the gammadetector 60 (e.g., in the Z-direction indicated on FIG. 7E). Inparticular, in the illustrated arrangement, eluate-receiving container56 and gamma detector 60 are arranged coaxially along their lengthsabout axis 160.

In general, ensuring that eluate-receiving container 56 is appropriatelyand repeatably positionable relative to gamma detector 60 can helpensure that gamma emissions measured by gamma detector 60 are accurateand appropriately calibrated. If eluate-receiving container 56 ispositioned too close to gamma detector 60, small changes in theseparation distance between the two components (e.g., aseluate-receiving container 56 is removed and reinserted into thirdcompartment 106) can lead to measurement inconsistencies by the gammadetector. By contrast, if eluate-receiving container 56 is positionedtoo far away from gamma detector 60, it may be challenging for the gammadetector to accurately detect low level gamma emissions.

In some examples, eluate-receiving container 56 is received in thirdcompartment 106 such that a bottom-most surface of the container isspaced a distance from the top of gamma detector 60. For example, abottom-most surface of eluate-receiving container 56 may be positioned adistance 162 from gamma detector. The separation distance 162 may rangefrom 5 millimeters to 100 millimeters, such as from 8 millimeters to 65millimeters, or from 10 millimeters to 30 millimeters. In some examples,the separation distance 162 is defined relative to the overall length ofeluate-receiving container 56. For example, the separation distance 162may range from 0.1 to 1.5 times the overall length of eluate-receivingcontainer 56, such as from 0.2 to 0.5 times the overall length of theeluate-receiving container. For instance, in the example whereeluate-receiving container 56 has a length of approximately 80millimeters and the separation distance is 0.25 times the overall lengthof the container, separation distance 162 can be approximately 20millimeters.

In some examples, eluate-receiving container 56 is positionable insideof third compartment 106 without having an intermediate structurepositioned between the container and gamma detector 60. Thirdcompartment 106 may have an interior ridge, rim, or other supportstructure on which eluate-receiving container 56 can be positioned orotherwise supported to hold the container in the compartment above thegamma detector 60. In other examples, an insert 164 may be positioned inthird compartment 106 between eluate-receiving container 56 and gammadetector 60. The insert 164 may serve different functions, such as aliquid collection barrier for radioactive eluate inadvertently spilledout of eluate-receiving container 56 and/or a positioning structure toposition eluate-receiving container 56 in compartment 106 at acontrolled location relative to gamma detector 60.

When used, insert 164 may be permanently mounted in third compartment106 or may be insertable into and removable from the compartment. Forexample, insert 164 may be a structure that has a closed bottom end andis removable from third compartment 106 (via the open top end of thecompartment). Insert 164 can collect radioactive eluate (or its decayproduct) that is inadvertently spilled and prevent the liquid fromfalling on gamma detector 60.

To retain insert 164 in third compartment 106, sidewall 106A may have aninwardly extending support means (a support means that extends towards acenter of the compartment). In different examples, the support means maybe a shoulder, a ridge, and/or a different inwardly protruding element.In the illustrated example, sidewall 106A has an inwardly extendingridge 166 on which a bottom surface of insert 164 may rest (or, ininstances where insert 164 is not used, a bottom of eluate-receivingcontainer 56 may rest). Additionally or alternatively, insert 164 mayhave a collar 168 extending outwardly from its body that is configuredto rest on the rim defining the opening of third compartment 106.Independent of the specific features utilized to retain insert 164 inthird compartment 106, the insert may hold the eluate-receivingcontainer 56, when the inserted therein, at a fixed position andorientation with respect to gamma detector 60. This can help ensurerepeatable measurements using gamma detector 60.

As discussed above with respect to FIG. 6 , system 10 can be used togenerate radioactive eluate that is infused (injected) into a patient,e.g., during a diagnostic imaging procedure. In practice, system 10 mayoperate in multiple modes of operation, one of which is a patientinfusion mode. System 10 may deliver radioactive eluate to a patientduring the patient infusion mode. System 10 may also generateradioactive eluate in one or more other modes in which the eluate is notdelivered to a patient, e.g., to help ensure the safety, quality, and/oraccuracy of radioactive eluate supplied during a subsequent patientinfusion.

As one example, system 10 may be subject to periodic quality control(QC) checks where the system is operated without having infusion tubing70 connected to a patient line 72. During a quality control mode ofoperation, radioactive eluate produced by system 10 may be analyzed todetermine the radioactivity of one or more species of radioisotopespresent in the radioactive eluate. If the activity level of one or moreradioisotopes exceeds a predetermined/threshold limit, system 10 may betaken out of service to prevent a subsequent patient infusion procedureuntil the activity level of one or more radioisotopes in the radioactiveeluate produced using the system are back within allowable limits.

For example, when the radioisotope generator 52 is implemented as astrontium-rubidium radioisotope generator, radioactive eluate producedusing the generator may be evaluated to determine if radioactivestrontium is releasing from the generator as eluant flows across and/orthrough the generator. Since strontium has a longer half-life thanRb-82, the amount of strontium infused into a patient with radioactiveeluate is typically minimized. The process of determining the amount ofstrontium present in the radioactive eluate may be referred to asbreakthrough testing since it may measure the extent to which strontiumis breaking through into the radioactive eluate.

As another example, system 10 may be subject to periodic constancychecks in which the system is again operated without having infusiontubing 70 connected to patient line 72. During a constancy evaluationmode of operation, activity measurements made using beta detector 58 maybe evaluated, e.g., cross checked, to determine whether the system isproducing accurate and precise measurements. If activity measurementsmade using beta detector 58 deviate from measurements made using avalidating apparatus, e.g., by more than a predetermined/thresholdamount, the system be recalibrated to help ensure efficacious andaccurate operation of system 10.

FIG. 8 is a flow diagram of an example technique that may be used toperform a patient infusion procedure to infuse radioactive liquid into apatient, e.g., during a diagnostic imaging procedure. For example, thetechnique of FIG. 8 may be used by system 10 to generate radioactiveeluate and infuse the radioactive eluate into a patient. The techniqueof FIG. 8 will be described with respect to system 10, and moreparticularly the arrangement of exemplary components described withrespect to FIG. 6 above, for purposes of illustration. However, itshould be appreciated that the technique may be performed by systemshaving other arrangements of components and configurations, as describedherein.

To initiate a patient infusion procedure, an operator may interact withsystem 10 to set the parameters of the infusion and to initiate theinfusion procedure. System 10 may receive parameters for the infusionvia user interface 16, via a remote computing device communicativelycoupled to system 10, or through yet other communication interfaces.Example parameters that may be set include, but are not limited to, thetotal activity to be dosed to a patient, the flow rate of radioactiveeluate to be dosed to the patient, and/or the volume of radioactiveeluate to be dosed to the patient. Once the appropriate parametersestablishing the characteristics of the infusion procedure areprogrammed and stored, system 10 may begin generating radioactive eluatethat is infused into the patient.

As shown in the example of FIG. 8 , a patient infusion procedure maystart by controlling second multi-way valve 74 to place radioisotopegenerator discharge line 75 in fluid communication with waste container54 via waste line 76 (200). If second multi-way valve 74 is initiallypositioned so radioisotope generator discharge line 75 is in fluidcommunication with waste container 54, controller 80 may control system10 to proceed with the infusion procedure without first actuating thevalve. However, if second multi-way valve 74 is positioned soradioisotope generator discharge line 75 is in fluid communication withinfusion tubing 70, controller 80 may control second multi-way valve 74(e.g., by controlling an actuator associated with the valve) to placethe radioisotope generator discharge line in fluid communication withthe waste container. In some examples, controller 80 receives a signalfrom a sensor or switch associated with second multi-way valve 74indicating the position of the valve and, correspondingly, which lineradioisotope generator discharge line 75 is in fluid communication withthrough the valve.

In addition to or in lieu of controlling second multi-way valve 74,controller 80 may check the position of first multi-way valve 64 and/orcontrol the valve to change the position of the valve before proceedingwith the patient infusion procedure. For example, if first multi-wayvalve 64 is positioned to direct eluant through bypass line 68,controller 80 may control the valve (e.g., by controlling an actuatorattached to the valve) to place eluant line 62 in fluid communicationwith the radioisotope generator inlet line 66. In some examples,controller receives a signal from a sensor or switch associated withfirst multi-way valve 64 indicating the position of the valve and,correspondingly, which line eluant line 62 is in fluid communicationwith the valve.

With first multi-way valve 64 positioned to direct eluant throughradioisotope generator inlet line 66 and second multi-way valve 74positioned to direct radioactive eluate from radioisotope generatordischarge line 75 to waste container 54, controller 80 can control pump40 to pump eluant from eluant reservoir 50. Under the operation ofcontroller 80, pump 40 can pump eluant from eluant reservoir 50 throughradioisotope generator 52, and thereby generate the radioactive eluatevia elution through the generator. In different examples, pump 40 maypump eluate at a constant flow rate or a flowrate that varies over time.In some examples, pump 40 pumps eluant at a rate ranging from 10milliliters/minute to 100 mL/minute, such as a rate ranging from 25mL/minute to 75 mL/minute. Radioactive eluate generated typically flowsat the same rate as the rate at which pump 40 pumps eluant.

As eluant flows through radioisotope generator 52, a radioactive decayproduct of a parents radioisotope bound in the generator may release andenter the flowing eluant, thereby generating the radioactive eluate. Thetype of eluant used may be selected based on the characteristics of theparent radioisotope and support material used for radioisotope generator52. Example eluants that may be used include aqueous-based liquids suchas saline (e.g., 0.1-1 M NaCl). For example, in the case of astrontium-rubidium radioisotope generator, a Normal (isotonic) salinemay be used as an eluant to elute Rb-82 that has decayed from Sr-82bound on a support material.

Radioactive eluate generated by radioisotope generator 52 can beconveyed to beta detector 58, allowing the radioactivity level (alsoreferred to as activity) of the eluate to be determined based onmeasurements made by the beta detector (204). In some configurations,radioactive eluate is supplied to tubing or a reservoir positionedproximate to beta detector 58, allowing the beta detector to measurebeta emissions emanating from a stopped and static volume of fluidpositioned in front of the detector. In other configurations, betadetector 58 can detect beta emissions emanating from radioactive eluateflowing through tubing positioned proximate to the detector. Forexample, beta detector 58 may detect beta emissions emanating fromradioactive eluate as the eluate flows through radioisotope generatordischarge line 75 to waste container 54. Controller 80 may receive asignal from beta detector 58 indicative of the beta emissions measuredby the beta detector.

Controller 80 may determine the activity of the radioactive eluate basedon the beta emissions measured by beta detector 58. For example,controller 80 may compare a magnitude of the beta emissions measured bybeta detector 58 to calibration information stored in memory relatingdifferent beta emission levels to different radioactive eluate activitylevels. Controller 80 can then determine the activity of the radioactiveeluate with reference to the calibration information and the betaemissions measured by beta detector 58 for the current radioactiveeluate flowing through radioisotope generator discharge line 75. Withall measurements made by system 10, controller 80 may account forradioactive decay between the radioisotope generator and a respectivedetector as the radioactive eluate travels through one or more tubinglines.

Because beta emissions from different radioisotopes are not easilydistinguishable from each other, controller 80 may not be able toresolve what portion of the measured activity is attributable to oneradioisotope as opposed to one or more other radioisotopes that may bepresent in the radioactive eluate. In instances where the radioactivedecay product present in the radioactive eluate is assumed to be thepredominant radioisotope species, controller 80 may set the measuredactivity of the radioactive eluate as the activity corresponding to theradioactive decay product. For example, in the case of a strontiumrubidium radioisotope generator, the activity of radioactive eluatedetermined using beta detector 58 may be assumed to be the activity ofRb-82 present in the radioactive eluate. This is because the activity ofany other radioisotopes that are present in the radioactive eluate maybe assumed to be significantly (e.g., orders of magnitude) smaller thanthe activity of Rb-82 present in the radioactive eluate.

In some examples, pump 40 continuously pumps eluant through radioisotopegenerator and radioactive eluate is delivered to waste container 54until the activity level of the radioactive eluate reaches a thresholdlevel. Radioactive eluate generated by radioisotope generator 52 afterthe generator has been inactive for a period of time may initially havea lower activity than radioactive eluate generated during continuedelution of the generator. For example, the activity of bolus radioactiveeluate produced using generator 52 may follow an activity curve thatvaries based on the volume of eluant passed through the generator andthe time since the start of the elution. As additional eluant is flowedthrough the radioisotope generator and time progresses, the activity maydecrease from the peak activity to an equilibrium.

In some examples, radioactive eluate generated by radioisotope generator52 is supplied to waste container 54 until the radioactive eluatereaches a minimum threshold activity value. The minimum thresholdactivity value can be stored in a memory associated with controller 80.In operation, controller 80 can compare the current activity of theradioactive eluate produced using generator 52 to the activity stored inmemory (206). Controller 80 may determine when to actuate secondmulti-way valve 74 to direct radioactive eluate from waste container 54to infusion tubing 70, and correspondingly patient line 72, based on thecomparison (208).

Since the peak activity of radioactive eluate generated by radioisotopegenerator 52 may vary over the service life of the generator, theminimum activity threshold may be set relative to one or more previouselution/infusion procedures performed by the radioisotope generatorsystem. For example, for each elution performed by system 10, controller80 may store in a memory associated with the controller a peakradioactivity detected during that elution, e.g., as measured via betadetector 58. During a subsequent elution, controller 80 may referencethe peak radioactivity, which may also be considered a maximumradioactivity, measured during a prior elution. Controller 80 may usethat maximum radioactivity from the prior run as a threshold forcontrolling the radioisotope generator during the subsequent run. Insome examples, the threshold is a percentage of the maximumradioactivity measured during a prior elution run, such as an immediateprior elution run. The immediate prior elution run may be the elutionrun performed before the current elution run being controlled withoutany intervening elution having been performed between the twoevolutions. For example, the threshold may be an activity value fallingwithin a range from 5% to 15% of the magnitude of maximum radioactivitydetected during a prior elution run, such as from 8% to 12% of themagnitude of maximum activity, or approximately 10% of the magnitude ofthe maximum activity. In other examples, the threshold may not bedetermined based on a prior radioactivity measurement measured usingsystem 10 but may instead be a value stored in a memory associated withcontroller 80. The value may be set by a facility in charge of system10, the manufacturer of system 10, or yet other party with control oversystem 10.

In the example of FIG. 8 , controller 80 controls second multi-way valve74 to divert radioactive eluate from waste container 54 to the patientvia infusion tubing 70 and patient line 72 connected to the infusiontubing (210). Upon determining that the activity of radioactive eluateflowing through radioisotope generator discharge line 75 via betadetector 58 has reached the threshold (e.g., equals or exceeds thethreshold), controller 80 may control second multi-way valve 74 (e.g.,by controlling an actuator associated with the valve) to deliver theradioactive eluate to the patient. Pump 40 may continue pumping theeluant through radioisotope generator 52, thereby delivering radioactiveeluate to the patient, until a desired amount of radioactive eluate hasbeen delivered to the patient.

In some examples, the desired amount of radioactive eluate is a setvolume of eluate programmed to be delivered to the patient. Controller80 can determine the volume of radioactive eluate delivered to thepatient, e.g., based on knowledge of the rate at which pump 40 pumps andthe duration the pump has pumped radioactive eluate. Additionally oralternatively, system 10 may include one or more flow sensors providingmeasurements to controller 80 concerning the volume of eluant and/orvolume of radioactive eluate flowing through one or more tubing lines ofthe system.

In some examples, controller 80 tracks the cumulative volume ofradioactive eluate generated by radioisotope generator 52, e.g., fromthe time at which the generator is installed in the system 10.Controller 80 may track the volume of radioactive eluate generatedduring patient infusion procedures as well as other modes of operationwhere radioactive eluate is generated but may not be supplied to apatient, e.g., during QC testing. In some examples, controller 80compares the cumulative volume of radioactive eluate generated byradioisotope generator 52 to an allowable limit and prevents at leastany further patient infusion of radioactive eluate using the generatorwhen the cumulative volume is determined to exceed (e.g., be equal to orgreater than) the allowable limit. In these configurations, thecumulative volume delivered by the radioisotope generator can act as acontrol point for determining when the generator should be taken out ofservice. While the allowable limit can vary based on a variety offactors such as the size and capacity of the radioisotope generator, insome examples, the allowable limit is less than 250 L, such as less than150 L, less than 100 L, less than 50 L, or less than 25 L. For example,the allowable limit may range from 5 L to 100 L, such as from 10 L to 60L, from 15 L to 40 L, or from 17 L to 30 L. In one particular example,the allowable limit is 17 L. In another particular example, theallowable limit is 30 L. System 10 can have hardware and/or softwarelocks that engage to prevent a subsequent patient infusion procedureonce the allowable limit is reached. For example, controller 80 mayprevent pump 40 from pumping eluant once the allowable limit has beenexceeded.

In addition to or in lieu of controlling the desired amount ofradioactive eluate based on the volume of eluate delivered to thepatient, controller 80 may control the desired amount of radioactiveeluate based on the cumulative amount of radioactivity delivered to thepatient (e.g., adjusting for radioactive decay during delivery).Controller 80 may control pump 40 to deliver eluant to radioisotopegenerator 52, thereby delivering radioactive eluate to the patient,until the cumulative amount of radioactivity delivered to the patientreaches a set limit. Controller 80 can determine the cumulative amountof radioactivity delivered to the patient by measuring the activity ofthe radioactive eluate via beta detector 58 during the delivery of theradioactive eluate to the patient. When controller 80 determines thatthe set amount of radioactivity has been delivered to the patient,controller 80 may control pump 40 to cease pumping the eluant and/orcontrol one or more valves in system 10 to redirect flow through thesystem.

In some examples, controller 80 controls first multi-way valve 64 toredirect eluant flowing through system 10 from radioisotope generatorinlet line 66 to bypass line 68. Controller 80 may or may not controlsecond multi-way valve 74 to place radioisotope generator discharge line75 in fluid communication with the waste line 76 instead of infusiontubing line 70. Controller 80 may control pump 40 to pump eluant throughbypass line 68 into infusion tubing 70 and patient line 72. Controller80 may control the pump to pump a volume of eluant through the linessufficient to flush residual radioactive eluate present in the linesfrom the lines into the patient. This may help remove residual sourcesof radioactivity from the environment surrounding the patient which mayotherwise act as interference during subsequent diagnostic imaging.Independent of whether controller 80 controls system 10 to provide aneluant flush following delivery of radioactive eluate to the patient,controller 80 can terminate operation of pump 40 to terminate thepatient infusion procedure (212).

As noted above, system 10 may be used to generate and deliverradioactive eluate in other applications in which infusion tubing 70 isnot connected to a patient. As one example, system 10 may generateradioactive eluate that is subject to quality control evaluation duringa quality control mode of operation. During the quality control mode ofoperation, radioactive eluate produced by system 10 may be analyzed todetermine the radioactivity of one or more species of radioisotopespresent in the radioactive eluate. In practice, when eluant is passedthrough a radioisotope generator containing a parent radioisotope boundon a support material, a daughter decay product radioisotope that bindsless tightly to the support material than the parent radioisotope canrelease into the eluant to form the radioactive eluate. One or moreother radioisotopes besides the daughter decay product intended to beeluted into the eluant may also enter the liquid. Periodic qualitycontrol evaluation of the radioactive eluate may be performed todetermine the activity level of these one or more other radioisotopes tohelp ensure that the activity level does not exceed a determine limit.

For example, in the case of a strontium-rubidium radioisotope generator,when eluant is passed through the generator, Rb-82 may be generated as aradioactive decay product from Sr-82 contained in the radioisotopegenerator, thereby generating the radioactive eluate. The eluate maycontain radioisotopes besides Rb-82, with the number and magnitude ofthe radioisotopes varying, e.g., based on the operational performance ofthe generator. For example, as the generator is used to generate dosesof Rb-82, Sr-82 and/or Sr-85 may release from the generator and alsoenter the eluate. As another example, cesium-131 may enter the eluate intrace amounts. Accordingly, the total amount of radioactivity measuredfrom the radioactive eluate may not be attributable to one particularradioisotope but may instead be the sum amount of radioactivity emittedby each of the different radioisotopes present in the eluate.

During quality control evaluation, the activity of one or moreradioisotopes present in the radioactive eluate (e.g., in addition to orin lieu of the decay product targeted for generation by the radioisotopegenerator) may be determined and compared to one or more allowablethresholds. FIG. 9 is a flow diagram of an example technique that may beused to perform a quality control procedure. For example, the techniqueof FIG. 9 may be used by system 10 to help ensure that radioactiveeluate generated by radioisotope generator 52 meets the standards setfor patient infusion. As with FIG. 8 , the technique of FIG. 9 will bedescribed with respect to system 10, and more particularly thearrangement of exemplary components described with respect to FIG. 6above, for purposes of illustration. However, it should be appreciatedthat the technique may be performed by systems having other arrangementsof components and configurations, as described herein.

In the technique of FIG. 9 , controller 80 can control system 10 todeliver radioactive eluate to the eluate-receiving container 56positioned proximate to a gamma detector 60 (220). To initiate theprocess, an operator may insert eluate-receiving container 56 into thirdcompartment 106 of shielding assembly 28 and close third door 106D toenclose the container in the compartment. Before or after positioningthird door 106D over the opening of the third compartment 106, theoperator can insert the end of infusion tubing 70 into theeluate-receiving container 56 to place the infusion tubing in fluidcommunication with the eluate-receiving container. For example, theoperator may insert eluate-receiving container 56 in the thirdcompartment 106 of shielding assembly 28, position third door 106D overthe opening of the compartment through which the eluate-receivingcontainer was inserted, and then insert the terminal end of infusiontubing line 70 through opening 158 of the door. In some configurations,the terminal end of infusion tubing line 70 includes a needle such thatinserting the infusion tubing line 70 through the opening in the thirddoor involves inserting the needle through the opening. Theeluate-receiving container 56 may or may not include a septum that ispierced by the needle on the terminal end of infusion tubing line 70 toplace the infusion tubing line in fluid communication with theeluate-receiving container. Alternatively, the eluate-receivingcontainer 56 in infusion tubing line 70 may be connected using a varietyof different mechanical connection features such as threaded connectors,Luer lock connectors, or yet other types of mechanical joining features.

Independent of how infusion tubing line 70 is placed in fluidcommunication with eluate-receiving container 56, the resultingarrangement may place radioisotope generator 52 in fluid communicationwith the eluate-receiving container via second multi-way valve 74. Thatis, when arranged to perform a quality control elution, the outlet ofinfusion tubing 70 can be placed in communication with eluate-receivingcontainer 56 and not in communication with patient line 72 or anypatient connected to the patient line. When so arranged, radioactiveeluate generated by radioisotope generator 52 can be supplied toeluate-receiving container 56 for evaluation by gamma detector 60instead of being delivered to a patient during a patient infusionprocedure.

Once system 10 is suitably arranged to allow eluate-receiving container56 to receive radioactive eluate from radioisotope generator 52,controller 80 can control the system to generate radioactive eluate thatis supplied to the eluate-receiving container. In some examples,controller 80 initiates a quality control elution in response toinstructions received via user interface 16 by an operator to performthe quality control elution. For example, controller 80 may executesoftware that guides the operator through one or more steps toappropriately arrange the components of system 10 for the qualitycontrol elution and receives feedback (e.g., via sensors and/or theoperator via the user interface) confirming that the components areappropriately arranged before generating radioactive eluate. Controller80 can control system 10 to execute the quality control elutionimmediately after arranging the components of system 10 to perform theelution or at a delayed time after the components have been arranged forthe quality control elution.

In instances where the quality control procedure takes a comparativelylong time to execute, for example, an operator may set system 10 toperform a quality control elution at a time when the system is nottypically used for patient infusion procedures. For example, system 10may be set to perform a quality control procedure at a preset time inthe day, such as over the midnight hour or in the evening. As examples,system may be set to perform the quality control elution at a timebetween 5 PM in the evening and 7 AM the next day, such as between 8 PMin the evening and 6 AM the next day, or between 12 PM and 4 AM the nextday in the time zone where the system is located. The operator mayinstall eluate-receiving container 56 and/or tubing in place theeluate-receiving container in fluid communication with the tubing priorto leaving the system unattended. Thereafter, system 10 operating underthe control of controller 80 may execute the quality control procedureat a subsequent preprogrammed time. The quality control results may thenbe available to the operator when they return to the system.

Regardless of the time at which system 10 executes the quality controlelution, controller 80 can control pump 40 to pump eluant throughradioisotope generator 52, thereby generating the radioactive eluatethat is supplied to the eluate-receiving container. In some examples,radioactive eluate generated by radioisotope generator 52 is supplieddirectly to eluate-receiving container 56 via infusion tubing 70 withoutdiverting an initial portion of the radioactive eluate to wastecontainer 54. In other examples, radioactive eluate generated byradioisotope generator 52 is initially directed to waste container 54until a threshold level of activity is reached as determined via betadetector 58. Upon determining that radioactive eluate being generated byradioisotope generator 52 has reached a threshold level of activity,controller 80 can control second multi-way valve 74 to directradioactive eluate flowing from radioisotope generator discharge line 75to infusion tubing 70 (and eluate-receiving container 56 connectedthereto) instead of to waste container 54.

For example, controller 80 may follow steps 200-208 discussed above withrespect to FIG. 8 during a quality control elution to supply radioactiveeluate to eluate-receiving container 56. Controller 80 can divertradioactive eluate initially generated by radioisotope generator 52 towaste container 54 until the activity of the radioactive eluate asdetermined via beta emissions measured by beta detector 58 reaches athreshold. Upon the activity of radioactive eluate generated byradioisotope generator 52 reaching the threshold, controller 80 cancontrol multi-way valve 74 to direct the radioactive eluate toeluate-receiving container 56.

Pump 40 can continue supplying eluant to radioisotope generator 52 andthereby supply radioactive eluate to eluate-receiving container 56 untila desired amount of radioactive eluate is supplied to the container. Insome examples, the desired amount of radioactive eluate is apre-established volume of radioactive eluate, e.g., based on the size ofeluate-receiving container 56. Controller 80 can control pump 40 tosupply an amount of radioactive eluate to eluate-receiving container 56sufficient to at least partially, and in some cases fully, fill theeluate-receiving container with radioactive eluate. In some embodiments,eluate-receiving container 56 may be filled to greater than 50% of itsmaximum volume with radioactive eluate, such as from 50% to 100% of itsmaximum volume, greater than 75% of its maximum volume, or from 60% to90% of its maximum volume. The total volume to which eluate-receivingcontainer 56 is filled during a quality control procedure, which may bereferred to as a quality control (QC) threshold volume may be greaterthan 5 mL, such as from 5 mL to 100 mL or from 5 mL to 50 mL. Asexamples, the QC threshold volume may range from 10 mL to 20 mL, from 20mL to 30 mL, from 30 mL to 40 mL, from 40 mL to 50 mL, from 50 mL to 75mL, or from 75 mL to 100 mL. For example, in one specificationapplication, the QC threshold volume is about 50 mL.

In addition to or in lieu of controlling the amount of radioactiveeluate supplied to eluate-receiving container 56 based on volume,controller 80 may control the amount of radioactive eluate supplied tothe container based on activity measurements made by beta detector 58.As radioactive eluate flows past the beta detector 58 toeluate-receiving container 56, the beta detector can measure the betaemissions emitted by the radioactive eluate. Controller 80 can receive asignal from beta detector 58 indicative of the beta emissions measuredby beta detector 58 and may compare a magnitude of the beta emissionsmeasured by the beta detector to calibration information stored inmemory relating different beta emission levels to different radioactiveeluate activity levels. Controller 80 may determine a cumulative amountof activity delivered to eluate-receiving container 56 based on theactivity of the radioactive eluate measured by the beta detector and/orthe flow rate of the radioactive eluate (e.g., adjusting for radioactivedecay during delivery). Controller 80 can compare the cumulative amountof activity delivered to eluate-receiving container 56, which may bereferred to as an accumulated radioactive dose supplied to thecontainer, to one or more thresholds stored in a memory associated withthe controller.

For example, controller 80 may compare the cumulative amount of activitysupplied to eluate-receiving container 56 to a quality control (QC)threshold level stored in a memory associated with the controller. TheQC threshold level may be programmed, e.g., by an operator ormanufacturer of system 10. In some examples, the QC threshold level isgreater than 5 mCi, such as greater than 15 mCi. For example, the QCthreshold level may range from 5 mCi to 75 mCi, such as from 10 mCi to60 mCi, from 15 mCi to 50 mCi, or from 20 mCi to 40 mCi. In one specificexample, the threshold QC level is approximately 30 mCi. The thresholdQC level can be the total activity of the radioactive eluate supplied toeluate-receiving container 56 as measured by beta detector 58 and ascorrected for radioactive decay during delivery based on time andhalf-life. Where a single radioisotope is assumed to be the dominantsource of radioactivity, the threshold level may be assumed tocorrespond to that radioisotope. In the example of a strontium-rubidiumradioisotope generator where Rb-82 is expected to be the dominant sourceof activity in the radioactive eluate flowing past the beta detector 58,the threshold QC level activity may be designated as a threshold QClevel of Rb-82.

Upon determining that the accumulated radioactive dose of radioactiveeluate supplied to eluate-receiving container 56 has reached the QCthreshold level, controller 80 can control pump 40 to cease pumpingeluant through radioisotope generator 52. Accordingly, in theseexamples, the amount of activity delivered to eluate-receiving container56 can act as a control point for determining how much volume ofradioactive eluate to deliver to the container. Controller 80 may alsomonitor the volume of radioactive eluate delivered to eluate-receivingcontainer 56 and control pump 40 to cease pumping if theeluate-receiving container will exceed its maximum capacity, even if theQC threshold level has not been reached. In these circumstances,controller 80 may issue a user alert via user interface 16 indicating anissue with the quality control testing.

In the technique of FIG. 9 , gamma detector 60 measures gamma emissionsemitted by radioactive eluate supplied to eluate-receiving container 56(220). Gamma detector 60 can continuously measure gamma emissions, e.g.,during filling of eluate-receiving container 56 and/or after theeluate-receiving container has suitably filled with radioactive eluate.Alternatively, gamma detector 60 may periodically sample gammaemissions, e.g., at one or more times after eluate-receiving container56 has suitably filled with radioactive eluate.

In some examples, gamma detector 60 measures gamma emissions emanatingfrom radioactive eluate in eluate-receiving container 56 at least uponthe container being initially filled when the pump stopped pumpingradioactive eluate to the container. Gamma detector 60 can measure gammaemissions emanating from radioactive eluate in eluate-receivingcontainer at one or more times after the container has filled withradioactive eluate, in addition to or in lieu of measuring the gammaemissions upon the container being initially filled. For example, gammadetector 60 may measure gamma emissions emanating from radioactiveeluate in eluate-receiving container 56 after a period of timesufficient for substantially all the initial daughter radioisotope(e.g., Rb-82) in the radioactive eluate to decay.

In some examples, the period of time sufficient for substantially allthe initial daughter radioisotope to decay is at least 3 half-lives ofthe daughter radioisotope, such as at least 5 half-lives of the daughterradioisotope. In the case of Rb-82 which has a half-life of about 76seconds, the period of time may be greater than 15 minutes, such asgreater than 20 minutes, or greater than 30 minutes. For example, theperiod of time may range from 15 minutes to one hour, such as 25 minutesto 45 minutes. Controller 80 can control gamma detector 60 to measuregamma emissions emanating from radioactive eluate in theeluate-receiving container 56 after the period of time has passed fromthe filling of the eluate-receiving container. As noted above, gammadetector 60 may or may not continuously measure gamma emissionsemanating from the radioactive eluate both before and after the periodof time has passed.

The gamma emission energies measured by gamma detector 60 may varydepending on the type of radioisotope generator utilized forradioisotope generator 52 and, correspondingly, the gamma emissionenergies of specific radioisotopes produced by the generator. In someexamples, gamma detector 60 is implemented as a wide range detector thatdetects a large gamma spectrum. In other examples, gamma detector isimplemented as a narrow range detector or is windowed to detect acomparatively narrower gamma spectrum.

In some applications, such as when radioisotope generator 52 isimplemented as a strontium-rubidium radioisotope generator, gammadetector 60 may be configured to measure gamma emissions at least in arange from 400 kilo-electron volts (keV) to 600 keV, such as from 450keV to 550 keV, from 465 keV to 537 keV, or from 511 keV to 514 keV. Insome examples, gamma detector 60 measures gamma emissions at least at agamma emission energy of 511 keV and/or 514 keV. In general, the gammaemission energy ranges detected by gamma detector 60 may be setdepending on the gamma emission energies of one or more radioisotopes ofinterest for measurement.

Gamma detector 60 can send, and controller 80 can receive, a signalindicative of the gamma emissions measured by the gamma detector. In thetechnique of FIG. 9 , controller 80 determines the presence and/oractivity of one or more radioisotopes present in the radioactive eluatebased on the measured gamma emissions (224). Controller 80 may determinethe amount of activity associated with a particular energy line of thegamma spectrum which corresponds to a particular radioisotope, therebydetermining the activity of that radioisotope.

In general, activity may be reported in Becquerel (Bq) or Curie (Ci) andis a function of the composition of a particular radioisotope and theamount of the radioisotope in the radioactive eluate. To determine theamount of activity associated with a particular radioisotope, controller80 may identify a region of interest of the gamma spectrum encompassingthe energy line corresponding to that radioisotope and integrate thearea under the peak for that energy line. The region of interest may bea region defined between two different energy lines that includes thepeak of interest and bounds the region under which the peak area isintegrated to determine corresponding activity.

In the case of a strontium-rubidium radioisotope generator, controller80 may determine an activity of Sr-82 and/or Sr-85 and/or any otherdesired radioisotopes of interest. In some examples, controller 80 candetermine an activity of Sr-82 by determining an activity associatedwith the 511 keV line of the gamma spectrum. In general, the activity ofSr-82 may not be measured directly via gamma emissions but may bemeasured by measuring the activity of Rb-82, which is the decay productof Sr-82 and can emit gamma emissions at the 511 keV energy line. Ininstances where the gamma spectrum is measured after a period of timesufficient for substantially all initial Rb-82 present in theradioactive eluate supplied from radioisotope generator 52 to decay,Rb-82 emissions measured at the 511 keV energy line may be assumed to beRb-82 decayed from Sr-82 present in the radioactive eluate, therebyproviding a measurement of the Sr-82 activity. Controller 80 candetermine the net peak integral count in the region of interestencompassing the 511 keV line to determine the activity of Sr-82.Controller 80 may then store the determined activity of Sr-82 in amemory associated with the controller.

As another example, controller 80 can determine an activity of Sr-85 bydetermining an activity associated with the 514 keV line of the gammaspectrum. Controller 80 can determine the net peak integral count in theregion of interest encompassing the 514 keV line to determine theactivity of Sr-85. Controller 80 may then store the determined activityof Sr-85 in a memory associated with the controller.

In applications where both the activity of Sr-82 and Sr-85 aredetermined, controller can determine the respective activity of eachradioisotope by gamma spectrum analysis as discussed above.Alternatively, controller 80 may determine the activity of one of Sr-82or Sr-85 by gamma spectrum analysis as discussed above and determine theactivity of the other strontium radioisotope with reference to a ratiostored in memory relating the activity of Sr-82 to the activity ofSr-85. The activity of Sr-82 may be related to the activity ofstrontium-85 by a known radioisotope ratio, which may be stored inmemory associated with controller 80. Controller 80 can determine theactivity of one radioisotope by multiplying the determined activity ofthe other radioisotope by the stored ratio. In some examples, controller80 sums the determined activity of Sr-82 and the determined activity ofSr-85 to identify the total strontium activity in the radioactiveeluate.

If desired, controller 80 can identify the amount of activity associatedwith other radioisotopes in the radioactive eluate based on the gammaemission data received from gamma detector 60. Controller 80 canidentify region(s) of interest encompassing other gamma emission energylines corresponding to the radioisotopes and determine a net peakintegral count for each energy line. Each energy line may correspond toa particular radioisotope, and the correspondence between differentenergy lines and different radioisotopes may be stored in a memoryassociated with the controller. Additional details on gamma detectorarrangements and gamma emission processing can be found in US PatentPublication No. US2015/0260855, entitled “REAL TIME NUCLEAR ISOTOPEDETECTION,” the entire contents of which are incorporated herein byreference.

Activity measurements made for one or more radioisotopes in theradioactive eluate can be stored and/or used for variety of purposes inradioisotope generator system 10. In the example of FIG. 9 , controller80 determines if one or more of the radioisotopes exceeds an allowablelimit (226). Controller 80 can compare the determined activity of aparticular radioisotope to a threshold stored in memory associated withthe controller. For example, controller 80 may compare a determinedactivity of Sr-82 to an allowable limit for Sr-82 stored in memory. Asexamples, the allowable limit for Sr-82 may be a Sr-82 level of lessthan 0.05 μCi per millicurie of Rb-82, such as less than 0.02 μCi permillicurie of Rb-82, about 0.02 μCi per millicurie of Rb-82, less than0.01 μCi per millicurie of Rb-82, or about 0.01 μCi per millicurie ofRb-82. As another example, controller 80 may compare a determinedactivity of Sr-85 to an allowable limit for Sr-85 stored in memory. Asexamples, the allowable limit for Sr-85 may be a Sr-85 level of lessthan 0.5 μCi per millicurie of Rb-82, such as less than 0.2 μCi permillicurie of Rb-82, about 0.2 μCi per millicurie of Rb-82, less than0.1 μCi per millicurie of Rb-82, or about 0.1 μCi per millicurie ofRb-82.

The Rb-82 activity level used to evaluate whether the determinedactivity of Sr-82 and/or Sr-85 exceeds an allowable limit may be a Rb-82activity (e.g., maximum or minimum Rb-82 activity level) determined viathe beta detector 58 or gamma detector 60. In one application, the Rb-82activity level used to evaluate whether the determined activity of Sr-82and/or Sr-85 exceeds an allowable limit is a fixed value, such as about10 millicurie. In other examples, the fixed value of Rb-82 is in therange from 10 millicurie Rb-82 to 100 millicurie Rb-82, such as 20millicurie, 30 millicurie, 40 millicurie, 50 millicurie, 60 millicurie,70 millicurie, 80 millicurie, or 90 millicurie. In one embodiment,controller 80 determines strontium levels, as a ratio of Sr-82 (in μCOto Rb-82 (in mCi), with a true positive rate of at least 95% with a 95%confidence level, at 0.01 μCi Sr-82 per millicurie of Rb-82. In anotherembodiment, controller 80 determines detect strontium levels, as a ratioof Sr-85 (in μCO to Rb-82 (in mCi), with a true positive rate of atleast 95% with a 95% confidence level, at 0.1 Ki Sr-85 per millicurie ofRb-82.

System 10 can take a variety of different actions if the determinedactivity of one or more radioisotopes during a quality control procedureis determined to exceed an allowable limit. In some examples, controller80 may initiate a user alert (e.g., a visual, textual, mechanical (e.g.,vibratory), audible user alert) such as via user interface 16,indicating that a measured radioisotope in the radioactive eluateproduced using the radioisotope generator 52 has exceeded allowablelimit. Additionally or alternatively, controller 80 may control system10 to prevent a subsequent patient infusion procedure if it isdetermined that a radioisotope in the radioactive eluate has exceeded anallowable limit. System 10 can have hardware and/or software locks thatengage to prevent a subsequent patient infusion procedure once theallowable limit is reached. For example, controller 80 may prevent pump40 from pumping eluant once the allowable limit has been exceeded. Insome examples, controller 80 electronically transmits a messageindicating that a radioisotope in the radioactive eluate has exceededallowable limit to an offsite location, e.g., for monitoring and/orevaluating the operation of the radioisotope generator.

System 10 may be used to generate and deliver radioactive eluate in yetother applications in which infusion tubing 70 is not connected to thepatient, e.g., to help maintain the quality and accuracy of radioactiveeluate generated by the system. As yet another example, system 10 maygenerate radioactive eluate as part of a constancy evaluation toevaluate the accuracy and/or precision of activity measurements beingmade by beta detector 58. Since beta detector 58 may be used to controlthe cumulative amount of activity delivered to a patient during apatient infusion procedure, ensuring that the detector is appropriatelycalibrated can help ensure accurate dosing of radioactive eluate.

FIGS. 10-16 describe exemplary calibration and quality control (“QC”)test(s) that may be periodically performed on the infusion system, suchas dose calibration using beta detector 58 and/or calibration of gammadetector 60 to help ensure the reliability of measurements made by theinfusion system using one or both detectors. Each performance test maybe used to evaluate the accuracy and/or precision of activitymeasurements made by the detector undergoing testing. Corrective actionsuch as recalibration or system lockout may be taken if a test is foundto fall outside of an acceptable limit. Any test or combination of testsdescribed may be performed using beta detector 58, gamma detector 60, orboth beta detector 58 and gamma detector 60 as part of a quality controland/or calibration protocol.

For example, QC test(s) performed using the beta detector 58 may includea dose calibration test, a dose linearity test, a dose repeatabilitytest, a dose constancy test, and combinations thereof. QC test(s)performed using the gamma detector 60 may include a gamma detectorcalibration test, a gamma detector repeatability test, a gamma detectorlinearity test, and combinations thereof. In some examples, a columnwash is performed on radioisotope generator 52 prior to executing a QCtest or series of QC test. The column wash can involve pumping a fixedvolume of eluant through radioisotope generator 52 and directing theresulting eluate to waste container 54. The fixed volume may range from10 ml to 100 ml, such as from 25 ml to 75 ml, or from 35 ml to 65 ml.The column wash can push eluate that remained stationary in radioisotopegenerator 52 over time out of the generator and move the generatorchemistry out of the equilibrium state and into the steady state. Acolumn wash may be performed before any patient infusion procedure aswell.

When calibrating gamma detector 60, a detector energy window calibrationQC test may be performed with (e.g., prior to) any of the other QCtest(s) to be performed on the detector. A source of radioisotope thathas a gamma emission energy that is the same as or similar to the parentradioisotope contained in radioisotope generator 52 (e.g., strontium)can be positioned for gamma detector 60 to read gamma radiation emittedfrom the source. The source of radioisotope may have a gamma emissionenergy that is within plus or minus 30% of the gamma emission energy ofthe parent radioisotope contained in radioisotope generator 52, such asplus or minus 20%, plus or minus 10%, plus or minus 15%, plus or minus5%, plus or minus 1%, or plus or minus 0.5%. Example sources ofradioisotope that may be used include Sr-82, Sr-85, sodium-22, andcesium-137.

The radioisotope source can be introduced into third compartment 106.Operating under the control of controller 80, gamma detector 60 can readthe gamma spectrum emitted by the calibration source. Controller 80 cancalculate a difference between the calculated peak channel in the gammaspectrum and the expected peak channel. Controller 80 may determine ifthe determined difference deviates by more than a tolerable range. Invarious examples, the tolerable range may be plus or minus 20%, such asplus or minus 10%, or plus or minus 5%. Controller 80 may determine ifthe difference exceeds the tolerable range. Controller 80 may take avariety of actions if the determined difference exceeds the tolerablerange. For example, controller 80 may issue a user alert (e.g., the userinterface 16) informing an operator if the peak channel exceeds thetolerable range for the expected peak channel. Additionally oralternatively, controller 80 may initiate recalibration (e.g., byadjusting the voltage so the peak channel is aligned with expected peakchannel).

As another example when calibrating gamma detector 60, backgroundradiation may be measured by the gamma detector in the absence of aspecific radioisotope source being introduced into third compartment106. The background radiation may be measured after performing thedetector energy window calibration but prior to performing any other QCtest(s) or at other times during the QC protocol. For example, during adaily QC protocol, background radiation may be measured beforeperforming other QC tests without performing a detector energy windowcalibration. The background radiation measurement may ensure that thereare no gamma emitting sources external to system 10 emitting at a levelthat causes distortion or error of the gamma measurements made by gammadetector 60 during a QC test. Controller 80 may take a variety ofactions if excessive background gamma radiation is detected, includingthose actions described herein.

QC test(s) may be performed using beta detector 58 and/or gamma detector60 at appropriate frequencies to maintain the high quality operation ofsystem 10. In some examples, a full QC protocol is performed followinginstallation or replacement of a component (e.g., tubing line,radioisotope generator, detector), after a major repair is performed onthe system (e.g., one performed by a representative of the manufacturerof system 10) and/or annually as part of a preventive maintenance plan.Such a full protocol may involve performing a gamma detector energywindow calibration QC test, a background radiation test, a column wash,a gamma detector calibration test, a repeatability test, a gammadetector linearity test, a gamma detector constancy test, a doseconstancy test, a dose linearity test, and/or a dose repeatability test.

A smaller QC protocol may be performed on a more frequent basis. Such aprotocol may involve performing a background radiation test with thegamma detector, a column wash, dose constancy test using the betadetector along with parent radioisotope (e.g., strontium) level testusing the gamma detector, and a gamma detector constancy test.Independent of the specific QC test or protocol set of tests performed,the tests may be performed at any desired frequency, such as a QC periodranging from every day to every 50 days, such as from 4 to 45 days, 4 to10 days, 11 to 17 days, 18 to 24 days, 25 to 31 days, 32 to 38 days, or39 to 45 days, or at approximately daily, 7 days, 14 days, 21 days, 28days, 35 days, or 42 days. When performing any QC test described hereinwhere eluate is passed through tubing, the test may be conducted at oneor more flow rates (in which case the test may be repeated at multipleflow rates. The flow rates can range from 10 ml/min to 60 ml/min, suchas 20 ml/min, 35 ml/min, or 50 ml/min, although other flow rates can beused depending on the configuration of the system and/or desire of theuser.

FIG. 10 is a flow diagram of an example technique that may be used toperform a constancy check procedure. For example, the technique of FIG.10 may be used by system 10 to evaluate dose constancy using betadetector 58.

To perform dose constancy, controller 80 can control system 10 todeliver radioactive eluate to the eluate-receiving container 56positioned proximate gamma detector 60 (230). The process of initiatingthe constancy evaluation and delivering radioactive eluate toeluate-receiving container 56 can follow that described above withrespect to FIG. 9 in connection with the quality control evaluationprocedure. For example, to initiate the process, an operator may inserteluate-receiving container 56 into third compartment 106 of shieldingassembly 28 and place infusion tubing 70 in fluid communication with theeluate-receiving container, as discussed above.

Once system 10 is suitably arranged to allow eluate-receiving container56 to receive radioactive eluate from radioisotope generator 52,controller 80 can control the system to generate radioactive eluate thatis supplied to the eluate-receiving container. In some examples,controller 80 initiates a constancy elution in response to instructionsreceived via user interface 16 by an operator to perform the constancyelution. For example, controller 80 may execute software that guides theoperator through one or more steps to appropriately arrange thecomponents of system 10 for the constancy elution and receives feedback(e.g., via sensors and/or the operator via the user interface)confirming that the components are appropriately arranged beforegenerating radioactive eluate. Controller 80 can control system 10 toexecute the constancy elution immediately after arranging the componentsof system 10 to perform the elution or at a delayed time after thecomponents have been arranged for the constancy eluate, as discussedabove with respect to the quality control procedure in connection withFIG. 9 .

Controller 80 may follow steps 200-208 discussed above with respect toFIG. 8 during a quality control elution to supply radioactive eluate toeluate-receiving container 56. Controller 80 can divert radioactiveeluate initially generated by radioisotope generator 52 to wastecontainer 54 until the activity of the radioactive eluate as determinedvia beta emissions measured by beta detector 58 reaches a threshold.Upon the activity of radioactive eluate generated by radioisotopegenerator 52 reaching the threshold, controller 80 can control multi-wayvalve 74 to direct the radioactive eluate to eluate-receiving container56.

Pump 40 can continue supplying eluant to radioisotope generator 52 andthereby supply radioactive eluate to eluate-receiving container 56 untila desired amount of radioactive eluate is supplied to the container.When controller 80 controls pump 40 to supply radioactive eluate toeluate-receiving container 56 until a desired amount of radioactiveeluate is supplied to the container, the controller can determine thecumulative amount of radioactivity delivered to the eluate-receivingcontainer by measuring the activity of the radioactive eluate via betadetector 58 during the delivery of the radioactive eluate to thecontainer. Controller 80 can also account for radioactive decay betweenbeta detector 58 and eluate-receiving container 56 (e.g., between thetime when the activity is measured by beta detector 58 and the time whenthe activity is measured by gamma detector 60). Alternatively, thedesired amount of radioactive eluate may be a pre-established volume ofradioactive eluate and/or a cumulative amount of activity (e.g.,corresponding to a QC threshold) delivered to eluate-receiving container56, as also discussed above with respect to FIG. 9 .

As radioactive eluate flows past the beta detector 58 toeluate-receiving container 56, the beta detector can measure the betaemissions emitted by the radioactive eluate (232). Controller 80 canreceive a signal from beta detector 58 indicative of the beta emissionsmeasured by beta detector 58 and may compare a magnitude of the betaemissions measured by the beta detector to calibration informationstored in memory relating different beta emission levels to differentradioactive eluate activity levels. Controller 80 may determine acumulative amount of activity delivered to eluate-receiving container56, which may be referred to as an accumulated radioactive dose suppliedto the container, based on the activity of the radioactive eluatemeasured by the beta detector and/or the flow rate of the radioactiveeluate.

Upon determining a suitable amount of radioactive eluate has beensupplied to eluate-receiving container 56, e.g., that the accumulatedradioactive dose supplied to eluate-receiving container has reached athreshold level, controller 80 can control pump 40 to cease pumping theeluant through radioisotope generator 52. When radioactive eluate stopsbeing introduced into eluate-receiving container 56, the filling of thecontainer may be designated as being complete. This can establish an endof filling time utilized from which subsequent activity may bebenchmarked.

In the technique of FIG. 10 , gamma detector 60 measures gamma emissionsemitted by radioactive eluate supplied to eluate-receiving container 56(234). Gamma detector 60 can continuously measure gamma emissions, e.g.,during filling of eluate-receiving container 56 and/or after theeluate-receiving container has suitably filled with radioactive eluate.Alternatively, gamma detector 60 may periodically sample gammaemissions, e.g., at one or more times after eluate-receiving container56 has suitably filled with radioactive eluate.

In some examples, gamma detector 60 measures gamma emissions emanatingfrom radioactive eluate in eluate-receiving container 56 within aconstancy window, which may be a time window measured from the end ofthe filling of eluate-receiving container 56. For example, gammadetector 60 may measure gamma emissions emanating from radioactiveeluate in eluate-receiving container 56 within a constancy time windowranging from 0 seconds from the end of the filling of theeluate-receiving container to 1800 seconds after the end of the filling,such as from 500 seconds to 1500 seconds from the end of the filling,from 700 seconds to 1000 seconds from the end of the filling, or from793 seconds to 807 seconds from the end of the filling of theeluate-receiving container. Gamma detector 60 can measure gammaemissions emanating from radioactive eluate in eluate-receivingcontainer continuously during the duration of the constancy time windowor at one or more times within the constancy time window.

Gamma detector 60 can send, and controller 80 can receive, a signalindicative of the gamma emissions measured by the gamma detector.Controller 80 can further determine the activity of Rb-82 in theeluate-receiving container based on the gamma emissions measured bygamma detector 60, thereby providing an accumulated constancy gammaactivity measurement. Controller 80 may determine the amount of activityassociated with a 511 keV energy line and/or 776 keV energy line of thegamma spectrum which corresponds to Rb-82. For example, controller 80may determine the net peak integral count in a region of the gammaspectrum encompassing the 511 keV line and/or 776 keV line to determinethe activity of Rb-82. Controller 80 may then store the determinedactivity of Rb-82 in a memory associated with the controller.

In the technique of FIG. 10 , controller 80 compares the activity ofRb-82 determined using beta detector 58 to the activity of Rb-82determined using gamma detector 60, e.g., by calculating a constancyratio (236). For example, controller 80 may calculate a constancy ratiobased on the accumulated radioactive dose (or beta emission counts)measured by beta detector 58 and supplied to eluate-receiving container56 and the accumulated constancy gamma activity (or gamma emissioncounts) measured by gamma detector 60. The constancy ratio may becalculated at least by dividing the accumulated radioactive dose by theaccumulated constancy gamma activity.

In some examples, controller 80 further compares the determinedconstancy ratio to one or more thresholds stored in memory associatedwith the controller. For example, controller 80 may compare thedetermined constancy ratio to a reference constancy ratio stored inmemory. Controller 80 may determine if the determined constant ratiodeviates from the reference conference ratio by more than a tolerablerange. In various examples, the tolerable range may be plus or minus 20%of the reference constancy ratio, such as plus or minus 10% of thereference constancy ratio, or plus or minus 5% of the referenceconstancy ratio. Controller 80 may determine if the constancy ratioexceeds the tolerable range for the reference constancy ratio.Controller 80 may take a variety of actions if the determined constancyratio exceeds the tolerable range for the reference constancy ratio.

In some examples, controller 80 issues a user alert (e.g., the userinterface 16) informing an operator if the determined constancy ratioexceeds the tolerable range and/or the reference constancy ratio.Additionally or alternatively, controller 80 may initiate a calibrationcheck and/or dose recalibration of the system (238). In some examples,controller 80 initiates calibration check and/or dose calibration byexecuting software to automatically perform such check or calibration orby guiding the operator through steps to perform such check orcalibration. To perform a dose calibration, a controller associated withsystem 10 may generate and store in memory one or more coefficients orother calibration information that is subsequently used by the system toprocess data generated by beta detector 58 corresponding to the amountof activity measured by the detector.

In some examples, a dose recalibration is performed using a dosecalibrator external to and separate from system 10. The dose calibratormay itself be calibrated using a primary standard. Controller 80 mayguide an operator via user interface 16 by providing instructions to theoperator for generating a sample of radioactive eluate. The sample ofradioactive eluate can then be transported to the separate dosecalibrator and the activity of Rb-82 in the sample determined using thedose calibrator. Controller 80 may receive the determined activity ofRb-82 from the dose calibrator (e.g., by being wired or wirelesslyconnected to the dose calibrator and/or by operator entry of theinformation via user interface 16). Controller 80 can store thedetermined activity of Rb-82 from the dose calibrator in memory and/oruse the information to modify calibration settings used by system 10 toprocess data generated by beta detector 58 corresponding to the activityof radioactive eluate flowing through system 10.

As another example, controller 80 may use the activity of Rb-82determined using gamma detector 60 to modify calibration settings usedby system 10 to process data generated by beta detector 58. For example,controller 80 may store the activity of Rb-82 determined using gammadetector 60 in memory and/or use the information to modify calibrationsettings used by system 10 to process data generated by beta detector 58corresponding to the activity of radioactive eluate flowing throughsystem 10.

FIG. 11 is a flow diagram of an example technique that may be used tocheck the accuracy of activity measurements made by gamma detector 60.For example, the technique of FIG. 11 may be used by system 10 toevaluate whether gamma detector 60 is providing accurate and/or preciseactivity measurements of the radioactive eluate generated byradioisotope generator 52.

To perform a calibration and accuracy test on gamma detector 60, thegamma detector may be exposed to a calibration source having a known (orotherwise expected) level of activity (250). The calibration source maybe placed in third compartment 106 adjacent gamma detector 60 andstatically held in the third compartment for a period of time sufficientfor the gamma detector to measure the activity of the calibrationsource. For example, when the calibration source is a solid material,eluate-receiving container 56 can be removed from third compartment 106and the calibration source can be placed in the compartment.Alternatively, if the calibration material is in a liquid state, thecalibration material can be pumped into eluate-receiving container 56that is placed in the third compartment.

Typical calibration sources that may be used to evaluate the accuracy ofgamma detector 60 are NIST (National Institute of Standards andTechnology) traceable radioisotope standards. The calibration source maybe selected to have an activity level similar to that observed by gammadetector 60 during typical operation of system 10. For example, thecalibration source may have an activity level ranging from 0.01 μCi to 2mCi, such as from 0.05 to 1 mCi, from 0.1 μCi to 100 μCi, from 1 μCi to75 μCi, from 25 μCi to 65 μCi, from 0.1 μCi to 30 from 1 μCi to 15 orfrom 8 μCi to 12 μCi. The calibration source may have a known (orotherwise expected) activity level to which the activity level detectedby gamma detector 60 can be compared.

Example isotopes that can be used as a calibration source to evaluatethe accuracy of gamma detector 60 include, but are not limited to,Na-22, Cs-131, Ga-68, and Ge-68. The calibration source may be stored ina shielded well or transport container separate from shielding assembly28. The calibration source may be stored in its shielded housing on ornear system 10 and removed from its shielded housing and inserted intothird compartment 106 to perform an accuracy test. Alternatively, thecalibration source may be brought from an external site, for example ina shielded housing, for periodic calibration testing.

Controller 80 may execute software that guides the operator through oneor more steps to appropriately arrange the calibration source in thirdcompartment 106 of system 10 for the accuracy test. Controller 80 canfurther control gamma detector 60 to measure the activity level of thecalibration source received in third compartment 106 (252). Controller80 can control gamma detector 60 to measure the activity level of thecalibration source concurrent with or immediately after inserting thecalibration source in the compartment or at a delayed time after thesource has been placed in the compartment, as discussed above withrespect to the quality control procedure in connection with FIG. 9 .

After detecting gamma radiation emanating from the calibration sourcehaving the known activity, controller 80 may identify a gamma radiationspectrum region of interest from which the activity of the sample isdetermined. In the case of a Na-22 calibration source, the region ofinterest can encompass the 511 keV peak in a gamma ray spectrumgenerated from the sample. Controller 80 can determine the net peakintegral count for the region of interest to determine the amount ofactivity measured by gamma detector 60 at the energy line.

In the technique of FIG. 11 , controller 80 compares the measuredactivity of the calibration source to a known activity of thecalibration sample (254). System 10 may be informed of the knownactivity of the calibration source, e.g., by entering the known activityvia user interface 16. The activity of the calibration source receivedby controller 80 can then be stored in a memory associated with thecontroller. Controller 80 can account for the decay of the activity ofthe calibration source using the known half-life of the radionuclide.Controller 80 can compare the determined activity of the calibrationsource as measured by gamma detector 60 to the known activity stored inmemory. Controller 80 may determine if the determined activity deviatesfrom the known activity by more than an acceptable threshold. In someexamples, the acceptable threshold may be within plus or minus 10% ofthe known activity, such as within plus or minus 5% of the knownactivity, within plus or minus 3% of the known activity, within plus orminus 2% of the known activity, or within plus or minus 1% of the knownactivity.

Controller 80 may take a variety of actions if the determined activityof the calibration source measured by gamma detector 60 exceeds theacceptable threshold of the known activity of the calibration source. Insome examples, controller 80 issues a user alert (e.g., via userinterface 16) informing an operator of the determined activity exceedsthe acceptable threshold. Additionally or alternatively, controller 80may calculate and/or store calibration data (e.g., a calibration ratio)relating the measured activity of the calibration source measured usinggamma detector 60 to the known activity of the calibration source.Controller 80 can subsequently use this calibration information duringoperation to adjust activity measurements made using gamma detector 60.

FIG. 12 is a flow diagram of another example technique that may be usedto evaluate the repeatability or precision of activity measurements madeby gamma detector 60. The technique of FIG. 12 may be used by system 10to evaluate whether gamma detector 60 is providing consistent andrepeatable activity measurements across multiple sample acquisitions ofa sample at the same activity level.

In the technique of FIG. 12 , a repeatability test may be performed ongamma detector 60 by repeatedly exposing the gamma detector to the samecalibration source having a known level of activity (256). Thecalibration source used to perform the repeatability test may beselected from any of those discussed above with respect to the accuracytest described in connection with FIG. 11 . The calibration source maybe placed adjacent (e.g., near and/or in front of) gamma detector 60,e.g., by inserting the calibration source in third compartment 106 ofshielding assembly 28. The calibration source may be held statically infront of gamma detector 60 for a period of time sufficient for the gammadetector to measure the activity of the calibration source.

After detecting gamma radiation emanating from the calibration sourcehaving the known activity, controller 80 may determine the activity ofthe calibration source (258) as discussed above. The calibration sourcecan be removed from third compartment 106, held outside of thecompartment for a period of time, and reinserted back into thecompartment (260). That is, the calibration source may be inserted intoand removed from the third compartment multiple times. Alternatively,the calibration source may be left in third compartment 106 and theactivity of the calibration source measured multiple times. Operatingunder the control of controller 80, gamma emissions emitted by thecalibration source can be measured and the activity of the calibrationsource determined. For example, the gamma emissions emitted by thecalibration source can be measured each time the calibration source isinserted into third compartment 106 and/or multiple times while thecalibration source remains in the third compartment. As a result, theactivity of the calibration source can be repeatedly determined toevaluate the consistency with which gamma detector 60 measures a sampleat the same activity level.

In the technique of FIG. 12 , the activity of the calibration source maybe measured at least twice, such as at least 3 times, at least 5 times,or at least 10 times. For example, the activity of the calibrationsource may be measured from 2 times to 20 times, such as from 5 times to15 times.

After repeatedly measuring the activity of the calibration source adesired number of times, the technique of FIG. 12 includes comparingeach measured activity to an average of multiple of the measuredcalibration activities (262). In some examples, controller 80 determinesan average (e.g., mean, median) measured activity of the calibrationsample based on all of the measurements made during the test. Controller80 may further compare each individual measured activity determinedduring the test to the average measured activity and determine if anyone measured activity deviates from the average measured activity bymore than acceptable threshold. In some examples, the acceptablethreshold may be within plus or minus 10% of the average measuredactivity, such as within plus or minus 5% of the average measuredactivity, or within plus or minus 2% of the average measured activity.

If controller 80 determines that any one of the plurality of measuredactivities exceeds the average measured activity by more than theacceptable threshold, the controller may take action to indicate thatgamma detector 60 is not producing sufficiently repeatable results. Insome examples, controller 80 issues a user alert (e.g., via userinterface 16) informing an operator that gamma detector 60 is notproducing sufficiently repeatable results.

FIG. 13 is a flow diagram of an example technique that may be used toevaluate the linearity of activity measurements made by gamma detector60. Evaluation of detector linearity can determine if gamma detector 60is providing a response that is linearly related to the activity of thesample being measured over the activity range expected to be observed bygamma detector 60 during operation.

To evaluate the linearity of gamma detector 60, one or more (e.g.,multiple) calibration sources each having a known activity can be placedin front of gamma detector 60. Each individual calibration source (orsingle calibration source, if only one is used) can be selected to havea half-life effective to provide sufficient measurable decay over thetime span of measurement. If multiple calibration sources are used, themultiple sources can be selected so each specific calibration source hasa different activity level than each other calibration source, providinga range of activities over which gamma detector 60 measures gammaemissions. The linearity of the activities measured by gamma detector 60can be evaluated to determine the linearity of the detector.

The particular activities of the calibration sources used to evaluatethe linearity of gamma detector 60 may be selected to cover the range ofactivities expected to be observed by the gamma detector during normaloperation. For example, where system 10 is implemented so gamma detector60 measures a comparatively high level of daughter radioisotope and alsomeasures a comparatively low level of parent radioisotope in a sampleunder evaluation, the calibration sources may be selected to cover therange from the high radioisotope activity level to the low radioisotopelevel. In some examples, the activity of the calibration sources used tomeasure the linearity of gamma detector 60 may range from 0.01 μCi to 2mCi, such as from 0.05 to 1 mCi, from 0.1 μCi to 100 μCi, 0.05 μCi to 50μCi, or 0.1 μCi to 30 μCi.

The calibration sources used to perform the gamma detector linearitytest may be selected from any of those discussed above with respect tothe accuracy test described in connection with FIG. 11 . In someexamples, the same type of calibration source (e.g., Na-22) at differentactivity levels is used to test the linearity of gamma detector 60. Inother examples, multiple different types of calibration sources atdifferent activity levels are used to test the linearity of gammadetector 60. For example, one type of calibration source at differentactivity levels may be used to test the comparatively low end of theactivity range and another type of calibration source at differentactivity levels may be used to test the comparatively high end of theactivity range. For example, a solid calibration source (e.g., Na-22)may be used to evaluate the low end of the linearity range and a liquidcalibration source (e.g., daughter radioisotope such as Rb-82 generatedby generator 52) may be used to evaluate the high end of the linearityrange.

In the example of FIG. 13 , a calibration source having a first activitylevel can be placed in front of gamma detector 60, e.g., by insertingthe calibration source in third compartment 106 of shielding assembly 28(270). The calibration source may be held statically adjacent to gammadetector 60 for a period of time sufficient for the gamma detector tomeasure the activity of the calibration source. After detecting gammaradiation emanating from the calibration source having the firstactivity level, controller 80 can measure the activity level of thecalibration source (272) as discussed above and store the measuredactivity in a memory associated with the controller.

A calibration source having a second activity level different than thefirst activity can be placed in front of gamma detector 60, e.g., byinserting the calibration source in third compartment 106 of shieldingassembly 28 (274). Again, the calibration source may be held staticallyin front of gamma detector 60 for a period of time sufficient for thegamma detector to measure the activity of the calibration source. Afterdetecting gamma radiation emanating from the calibration source havingthe second activity level, controller 80 can measure the activity levelof the calibration source (274) as discussed above and store themeasured activity in a memory associated with the controller.

One or more additional calibration sources each having a differentactivity level than each other, and than the first and secondcalibration sources already measured by gamma detector 60, may also beplaced in front of the gamma detector (278). Gamma detector 60 maymeasure the activity of the additional calibration source(s) and storethe measured activity in a memory associated with the controller. Insome examples, at least three calibration sources are used havingdifferent activity levels over an expected activity range that gammadetector 60 is expected to measure during operation. In some otherexamples at least five calibration sources having different activitylevels are used.

After measuring the activity levels of a suitable number of calibrationsources, the technique of FIG. 13 involves linearly regressing the dataand determining an R-squared value for the measured activity values.R-squared is a statistical measure of how close the data are to a fittedregression line. Controller 80 may determine an R-squared value for themeasured activity values of the different calibration sources.Controller 80 may further compared the determined R-squared value to athreshold stored in memory. In some examples, the threshold may requirethe R-squared value be greater than 80%, such as greater than 90%,greater than 95%, or greater than 98%. If controller 80 determines thatthe R-squared value is below the required threshold, the controller maytake action to indicate that gamma detector 60 is not producingsufficiently linear results. In some examples, controller 80 issues auser alert (e.g., via user interface 16) informing an operator thatgamma detector 60 is not producing sufficiently linear results.

As noted, the calibration sources used to measure the linearity of gammadetector 60 may range in activity level from the comparatively highactivity levels associated with a daughter radioisotope (e.g., Rb-82) tocomparatively low activity levels associated with a parent radioisotopeand/or contaminant radioisotope (e.g., Sr-82, Sr-85). In some examples,system 10 operating under the control of controller 80 is configured toperform multiple gamma detector linearity tests, including one coveringthe high range of activity levels expected to be observed by gammadetector 60 and one covering the low range of activity levels expectedto be observed by the gamma detector.

In some applications when so configured, controller 80 may controlsystem 10 to generate radioactive eluate via radioisotope generator 52to provide a radioisotope source for testing one of the linearity ranges(e.g., the comparatively high activity range). Controller 80 may followsteps 200-208 discussed above with respect to FIG. 8 during a qualitycontrol elution to supply radioactive eluate to eluate-receivingcontainer 56. Controller 80 can divert radioactive eluate initiallygenerated by radioisotope generator 52 to waste container 54 until theactivity of the radioactive eluate as determined via beta emissionsmeasured by beta detector 58 reaches a threshold. Upon the activity ofradioactive eluate generated by radioisotope generator 52 reaching thethreshold, controller 80 can control multi-way valve 74 to direct theradioactive eluate to eluate-receiving container 56.

Gamma detector 60 can measure gamma emissions emitted by radioactiveeluate supplied to eluate-receiving container 56. Gamma detector 60 cancontinuously measure gamma emissions, e.g., during filling ofeluate-receiving container 56 and/or after the eluate-receivingcontainer has suitably filled with radioactive eluate. Gamma detector 60may periodically sample gamma emissions, e.g., at one or more timesafter eluate-receiving container 56 has suitably filled with radioactiveeluate.

The linearity of gamma detector 60 may be tested across a range ofactivity levels associated with the daughter radioisotope in theradioactive eluate supplied to the eluate-receiving container, e.g., asthe daughter radioisotope decays to progressively lower activity levels.To perform the gamma detector linearity testing across this range,activity levels measured by gamma detector 60 across multiplepre-determined periods following the end of elution may be used toevaluate linearity. In some embodiments of the present invention, themultiple pre-determined periods can range from 500 seconds to 1600seconds, from 600 seconds to 1300 seconds, from 700 seconds to 1200seconds, or from 750 seconds to 1100 seconds. For example, gammadetector 60 may make a first activity measurement within a time rangefrom 600 to 950 seconds following the end of elution, such as from 700to 800 seconds, from 725 to 775 seconds, or at approximately 750seconds. Gamma detector 60 may make a second activity measurement at alater time within a range from 650 to 1000 seconds following the end ofelution, such as from 750 to 850 seconds, from 775 to 825 seconds, or atapproximately 800 seconds. Gamma detector 60 may make a third activitymeasurement at a yet later time within a range from 950 to 1250 secondsfollowing the end of elution, such as from 1050 to 1150 seconds, from1075 to 1125 seconds, or at approximately 1100 seconds. Activitymeasurements at different time periods including earlier or later times(and/or additional measurements within the overall time) may be made andincluded as part of the linearity calculation as needed.

In either case, the resulting measured activity levels of radioactiveeluate in eluate-receiving container 56 made by gamma detector 60 can beevaluated for linearity. Controller 80 may linearly regress the data anddetermine an R-squared value for the measured activity values at thedifferent times. Controller 80 may further compared the determinedR-squared value to a threshold stored in memory, as discussed above.

To measure the linearity of gamma detector 60 across a comparatively lowrange of activity levels associated with the parent radioisotope and/orcontaminants in the radioactive eluate delivered to the eluate-receivingcontainer, external calibration sources (e.g., Na-22) may be insertedinto third compartment 106. The external calibration sources may rangein activity level from approximately 0.1 μCi to approximately 10 μCi,which may correspond to the range of parent radioisotope activity levelsthat may be observed by gamma detector 60 during operation. Thelinearity of activity measurements made using the external calibrationsources may be regressed and an R-squared value calculated, as discussedabove. Controller 80 may further compared the determined R-squared valueto a threshold stored in memory, as further discussed above.

FIG. 14 is a flow diagram of an example technique that may be used toperform a dose calibration using beta detector 58. To perform acalibration according to the example technique, an outlet of infusiontubing line 70 can be attached to an eluate collection container.Eluate-receiving container 56 may be used as the eluate collectioncontainer during calibration, or an eluate collection container having adifferent configuration can be used. For example, the eluate collectioncontainer attached to infusion tubing line 70 may be configured to beinserted into third compartment 106 of shielding assembly 28, intoanother shielded container, and/or directly into a dose calibratorconfigured to measure the activity of the contents therein.

To perform calibration, controller 80 can control system 10 to deliverradioactive eluate to the eluate collection container (292). The processof initiating the calibration and delivering radioactive eluate to theeluate collection container can follow that described above with respectto FIG. 9 in connection with the quality control evaluation procedure.For example, to initiate the process, an operator may attach infusiontubing line 70 to the eluate collection container and interact withsystem 10 (e.g., via user interface 16) to elute a sample of radioactiveRb-82 to the container. The eluate collection container may or may notbe inserted into a dose calibrator prior to initiating elution.

In some examples, infusion tubing line 70 extends from system 10 to aneluate collection container positioned in a dose calibrator located offboard the mobile cart (e.g., on a counter or table adjacent to thecart). In other configurations, system 10 may include an onboard dosecalibrator that is contained on the mobile cart and is movabletherewith. In either case, controller 80 may receive data generated bythe dose calibrator via wired or wireless communication with the dosecalibrator and/or via user entry using user interface 16. In someexamples, the eluate collection container is positioned in thirdcompartment 106 of shielding assembly 28 and gamma detector 60 is usedto generate data for dose calibration.

Once system 10 is suitably arranged to allow the eluate collectioncontainer to receive radioactive eluate from radioisotope generator 52,controller 80 can control the system to generate radioactive eluate thatis supplied to the eluate collection container. In some examples,controller 80 initiates a calibration elution in response toinstructions received via user interface 16 by an operator to performthe calibration elution. For example, controller 80 may execute softwarethat guides the operator through one or more steps to appropriatelyarrange the components of system 10 for the calibration elution andreceives feedback (e.g., via sensors and/or the operator via the userinterface) confirming that the components are appropriately arrangedbefore generating radioactive eluate. Controller 80 can control system10 to execute the calibration elution immediately after arranging thecomponents of system 10 to perform the elution or at a delayed timeafter the components have been arranged for the calibration elution, asdiscussed above with respect to the quality control procedure inconnection with FIG. 9 .

Controller 80 may follow steps 200-208 discussed above with respect toFIG. 8 during a quality control elution to supply radioactive eluate toeluate collection container. Controller 80 can divert radioactive eluateinitially generated by radioisotope generator 52 to waste container 54until the activity of the radioactive eluate as determined via betaemissions measured by beta detector 58 reaches a threshold. Upon theactivity of radioactive eluate generated by radioisotope generator 52reaching the threshold, controller 80 can control multi-way valve 74 todirect the radioactive eluate to eluate collection container.Alternatively, controller 80 may deliver an initial eluted volume ofeluate to the eluate collection container without first diverting towaste container 54.

Pump 40 can continue supplying eluant to radioisotope generator 52 andthereby supply radioactive eluate to the eluate collection containeruntil a desired amount of radioactive eluate is supplied to thecontainer. As radioactive eluate flows past the beta detector 58 to theeluate collection container, the beta detector can measure the betaemissions emitted by the radioactive eluate. Controller 80 can determinean activity of the eluate (294), for example by receiving a signal frombeta detector 58 indicative of the beta emissions measured by betadetector 58 and may compare a magnitude of the beta emissions measuredby the beta detector to calibration information stored in memoryrelating different beta emission levels to different radioactive eluateactivity levels. Controller 80 may determine a cumulative amount ofactivity delivered to eluate collection container, based on the activityof the radioactive eluate measured by the beta detector and/or the flowrate of the radioactive eluate.

In the technique of FIG. 14 , the activity of the eluate delivered tothe eluate collection container is also measured by a dose calibrator.The activity of the eluate received by the collection container may bemeasured continuously from filling of the container through completionof the calibration measurement or at one or more discrete time periodsduring calibration. For example, the activity of the eluate in thecontainer may be measured following the end of elution, when pump 40ceases pumping eluant through radioisotope generator 52 to generateeluate or controller 80 controls multi-way valve 74 to direct theradioactive eluate to waste container 54 instead of the eluatecollection container. In some examples, the activity of the eluate inthe eluate collection container is measured at least once between 1minute following the end of elution and 10 minutes following the end ofelution, such as between 2 minutes following the end of elution and 7minutes following the end of elution. In different examples, theactivity of the eluate may be measured at 2:30, 3:45, or 5:00 minutesafter the end of elution.

Controller 80 of system 10 (or another controller) can calculate acalibration ratio based on the cumulative activity of the eluatesupplied to the eluate collection container measured by beta detector 58and the corresponding activity measured by the dose calibrator (e.g.,along with the time the activity is measured). The controller maycalculate a ratio by dividing the activity measured by the external dosecalibrator by the cumulative activity measured by beta detector 58.Controller may adjust the activity measured by the dose calibrator toaccount for radioactive decay between the time of elution and when theactivity measurement was made using information indicative of the amountof time that passed between the end of elution and when the activitymeasurement was made. The controller may store the calibration ratio ina memory associated with the controller for reference and adjustment ofactivity measurements made by beta detector 58 during subsequent use.

In some examples, controller 80 compares the calculated calibrationratio to a previously calculated calibration ratio stored in memory(300). The prior calibration ratio may be that which was generatedduring the calibration test performed immediately prior to thecalibration being currently performed. Controller 80 may determinewhether the newly-calculated calibration ratio deviates from thepreviously calculated calibration ratio by more than acceptablethreshold. In some examples, system 10 requires the newly-calculatedcalibration ratio to be within plus or minus 10% of the previouslycalculated calibration ratio, such as within plus or minus 5% of thepreviously calculated calibration ratio, within plus or minus 2% of thepreviously calculated calibration ratio, or within plus or minus 1% ofthe previously calculated calibration ratio.

If the newly-calculated calibration ratio deviates from the previouslycalculated calibration ratio by more than the acceptable thresholdcontroller 80 may take action to indicate the discrepancy. In someexamples, controller 80 issues a user alert (e.g., via user interface16) instructing the user to repeat the calibration process. If, aftermultiple rounds of the performing the calibration procedure, thenewly-calculated calibration ratio continues to deviate from thepreviously calculated calibration ratio (the ratio that was lastaccepted by the system), controller 80 may issue a user alertinstructing the user to contact maintenance personnel, such as amanufacturer representative. Controller 80 may further prohibitcontinued use of the system and/or a patient infusion procedure untilthe system has been evaluated by an authorized representative.Controller 80 may provide such a response after at least two rounds ofattempted calibration, such as from 2 rounds to 8 rounds, or from 3rounds to 5 rounds.

In some examples, the calibration technique of FIG. 14 is performedmultiple times at different flow rates, and different calibration ratioscorresponding to each flow rate are stored in a memory associated withthe controller. For example, the calibration technique may be performedonce at a comparatively low flow rate, e.g., ranging from 5 ml/min to 35ml/min, such as from 15 ml/min to 25 ml/min, or at 20 ml/min. Thecalibration technique may also be performed at a comparatively high flowrate, e.g., ranging from 25 ml/min to 100 ml/min, such as from 40 ml/minto 60 ml/min, or at 50 ml/min. Controller 80 may execute software thatguides a user to perform the multiple iterations of calibration andfurther control pump 40 to pump at the different flow rates duringcalibration.

FIG. 15 is a flow diagram of an example technique that may be used toevaluate dose linearity using beta detector 58. Evaluation of doselinearity can determine if beta detector 58 is providing a response thatis linearly related to the activity of the sample being measured overthe activity range expected to be observed by beta detector 58 duringoperation.

One embodiment involves evaluating beta detector linearity wheremultiple calibration sources each having a known activity are placedover beta detector 58. The multiple calibration sources can be selectedso each specific calibration source has a different activity level thaneach other calibration source, providing a range of activities overwhich beta detector 58 measures beta emissions. The linearity of theactivities measured by beta detector 58 can be evaluated to determinethe linearity of beta detector 58.

The specific activities of the calibration sources used to evaluate doselinearity using beta detector 58 may be selected to cover the range ofactivities expected to be observed by the beta detector during normaloperation. For example, where system 10 is implemented so beta detector58 measures a comparatively high level of daughter radioisotope, thecalibration sources may be selected to cover the range of daughterradioisotope activity levels expected to be observed during operation.In some examples, the activity of the calibration sources used tomeasure dose linearity using beta detector 58 may range from 5 mCi to100 mCi, such as from 10 mCi to 50 mCi, or 15 mCi to 30 mCi.

Another embodiment involves evaluating dose linearity using betadetector 58 where liquid calibration sources are used by flowing theliquid calibration sources through the tubing line positioned adjacentbeta detector 58. For example, controller 80 may control system 10 togenerate radioactive eluate via radioisotope generator 52 to provide aradioisotope source for testing the dose linearity using beta detector58 (310). It is appreciated that dose linearity covers contributionsfrom more system components than beta detector linearity.

Controller 80 may follow steps similar to steps 200-208 discussed abovewith respect to FIG. 8 during a quality control elution to supplyradioactive eluate to eluate-receiving container 56. Controller 80 candivert radioactive eluate generated by radioisotope generator 52 andflowing past beta detector 58 during the dose linearity test to wastecontainer 54. Beta detector 58 can measure beta emissions emitted byradioactive eluate flowing through the tubing line positioned adjacentthe beta detector (312).

Controller 80 can control system 10 to generate radioactive eluatehaving different activity levels of daughter radioisotope to perform thedose linearity test (314). The activity of the eluate generated bysystem 10 may vary during the course of elution as the activity ramps upto a peak bolus and then attenuates to an equilibrium state. In someexamples, at three different activity levels of eluate are measured bybeta detector 58 during dose linearity testing. One of the activitylevels may range from 10 mCi to 20 mCi, such as 15 mCi. A second of theactivity levels may range from 20 mCi to 40 mCi, such as 30 mCi. A thirdof the activity levels may range from 50 mCi to 100 mCi, such as 60 mCi.Additional or different activity levels may be used for dose linearitytesting.

Beta detector 58 may measure the activity of the calibration sourcesand/or eluate samples at different activity levels and the measuredactivity can be stored in a memory associated with controller 80. Aftermeasuring the activity levels of a suitable number of calibrationsources and/or samples, the technique of FIG. 15 involves linearlyregressing the data and determining an R-squared value for the measuredactivity values (316). R-squared is a statistical measure of how closethe data are to a fitted regression line. Controller 80 may determine anR-squared value for the measured activity values of the differentcalibration sources. Controller 80 may further compare the determinedR-squared value to a threshold stored in memory. In some examples, thethreshold may require the R-squared value be greater than 80%, such asgreater than 90%, greater than 95%, or greater than 98%. If controller80 determines that the R-squared value is below the required threshold,the controller may take action to indicate that beta detector 58 is notproducing sufficiently linear results. In some examples, controller 80issues a user alert (e.g., via user interface 16) informing an operatorthat beta detector 58 is not producing sufficiently linear results.

In some examples where eluate samples having different activity levelsare used for dose linearity testing, the testing process may beperformed multiple times at different flow rates. For example, the doselinearity testing technique may be performed once at a comparatively lowflow rate, e.g., ranging from 5 ml/min to 35 ml/min, such as from 15ml/min to 25 ml/min, or at 20 ml/min. The dose linearity testingtechnique may also be performed at a comparatively high flow rate, e.g.,ranging from 25 ml/min to 100 ml/min, such as from 40 ml/min to 60ml/min, or at 50 ml/min. Controller 80 may execute software that guidesa user to perform the multiple iterations of the dose linearity testingand further control pump 40 to pump at the different flow rates duringtesting.

FIG. 16 is a flow diagram of an example technique that may be used toevaluate the repeatability or precision of activity measurements made bybeta detector 58. The technique of FIG. 16 may be used by system 10 toevaluate whether beta detector 58 is providing consistent and repeatableactivity measurements across multiple sample acquisitions of a sample atthe same activity level.

In the technique of FIG. 16 , a dose repeatability test may be performedusing beta detector 58 by repeatedly exposing the beta detector to thesame calibration source having a known level of activity. A liquidcalibration source may be passed through the tubing line positionedadjacent beta detector 58. For example, controller 80 may control system10 to generate radioactive eluate via radioisotope generator 52 toprovide a radioisotope source for testing the constancy of beta detector58 (320).

Controller 80 may follow steps similar to steps 200-208 discussed abovewith respect to FIG. 8 during a quality control elution to supplyradioactive eluate to eluate-receiving container 56. Controller 80 candivert radioactive eluate generated by radioisotope generator 52 andflowing past beta detector 58 during the constancy test to wastecontainer 54. Beta detector 58 can measure beta emissions emitted byradioactive eluate flowing through the tubing line positioned adjacentthe beta detector (322).

The target activity of the radioactive eluate flowing through the tubingline may range from 10 mCi to 100 mCi, such as from 20 mCi to 50 mCi, orfrom 25 mCi to 35 mCi. For example, the target activity level may be 30mCi, although other activity levels can be used. The radioactive eluatemay be supplied at flow rates ranging from 5 ml/min to 100 ml/min, suchas from 20 ml/min to 50 ml/min, although other flow rates can be used.

After detecting beta emissions emanating from the eluate flowing throughthe tubing line, controller 80 may determine the activity of thecalibration eluate (322). Controller 80 can cease generating radioactiveeluate and wait a period of time sufficient to allow radioisotopegenerator 52 to recover (324). Thereafter, controller 80 can againcontrol system 10 to generate radioactive eluate having the same targetactivity as that generated initially during constancy testing (326).System 10 may generate, and beta detector 58 may measure, at least twosamples of eluate having the target activity, such as at least 5, or atleast 10. For example, system 10 may generate, and beta detector 58 maymeasure, from 2 to 20 samples, such as from 5 to 15 samples.

After measuring the activity of repeated samples a desired number oftimes, the technique of FIG. 16 includes comparing each measuredactivity to an average of multiple of the measured calibrationactivities (328). In some examples, controller 80 determines an average(e.g., mean, median) measured activity of the calibration sample basedon all of the measurements made during the test. Controller 80 mayfurther compare each individual measured activity determined during thetest to the average measured activity and determine if any one measuredactivity deviates from the average measured activity by more thanacceptable threshold. In some examples, the acceptable threshold may bewithin plus or minus 10% of the average measured activity, such aswithin plus or minus 5% of the average measured activity, or within plusor minus 2% of the average measured activity.

If controller 80 determines that any one of the plurality of measuredactivities exceeds the average measured activity by more than theacceptable threshold, the controller may take action to indicate thatbeta detector 58 is not producing sufficiently repeatable results. Insome examples, controller 80 issues a user alert (e.g., via userinterface 16) informing an operator that beta detector 58 is notproducing sufficiently repeatable results.

The techniques described in this disclosure may be implemented, at leastin part, in hardware, software, firmware or any combination thereof. Forexample, various aspects of the described techniques may be implementedwithin one or more processors, including one or more microprocessors,digital signal processors (DSPs), application specific integratedcircuits (ASICs), field programmable gate arrays (FPGAs), or any otherequivalent integrated or discrete logic circuitry, as well as anycombinations of such components. The term “processor” may generallyrefer to any of the foregoing logic circuitry, alone or in combinationwith other logic circuitry, or any other equivalent circuitry. A controlunit comprising hardware may also perform one or more of the techniquesof this disclosure.

Such hardware, software, and firmware may be implemented within the samedevice or within separate devices to support the various operations andfunctions described in this disclosure. In addition, any of thedescribed units, modules or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

The techniques described in this disclosure may also be embodied orencoded in a non-transitory computer-readable medium, such as acomputer-readable storage medium, containing instructions. Instructionsembedded or encoded in a computer-readable storage medium may cause aprogrammable processor, or other processor, to perform the method, e.g.,when the instructions are executed. Non-transitory computer readablestorage media may include volatile and/or non-volatile memory formsincluding, e.g., random access memory (RAM), magnetoresistive randomaccess memory (MRAM), read only memory (ROM), programmable read onlymemory (PROM), erasable programmable read only memory (EPROM),electronically erasable programmable read only memory (EEPROM), flashmemory, a hard disk, a CD-ROM, a floppy disk, a cassette, magneticmedia, optical media, or other computer readable media.

The following examples may provide additional details about radioisotopedelivery systems in accordance with the disclosure.

Example 1

Sr-82 and Sr-85 samples covering the range of activity levels that maybe observed during operation of a strontium-rubidium radioisotopegenerator were compared using three exemplary measurement systems: a CZTgamma detector, a dose Calibrator, and a high-purity germanium gammadetector (HPGe). Ten activity readings were made across the range ofactivity levels for each of the detectors. The results are presented inTable 1 below.

TABLE 1 Comparison of measurements by the three detector systems Sr-82Level^(#) HPGe Gamma Detector Ratio CZT Gamma Detector Dose CalibratorSr-82 Sr-85 μCi/mCi Sr-82 Sr-85 Reading Sr-82 Sr-85 ID μCi % CV** μCi %CV Rb-82 μCi Error %* % CV** μCi μCi μCi % Error* μCi 1 7.0488 0.510.4061 0.1 0.2350 6.211 11.89 0.31 9.080 11.19 6.58 6.71 9.61 2 3.42970.7 5.0836 0.2 0.1143 3.098 9.67 0.44 4.529 5.63 3.31 3.54 4.84 3 0.76451.5 1.1258 0.4 0.0255 0.709 7.26 0.93 1.037 1.25 0.73 3.92 1.07 4 0.42852.0 0.6219 0.5 0.0143 0.39 8.98 1.25 0.570 0.74 0.43 −1.48 0.64 5 0.24502.6 0.3506 0.7 0.0082 0.223 8.98 1.64 0.326 0.38 0.22 8.86 0.33 6 0.14203.4 0.2085 0.8 0.0047 0.131 7.75 2.14 0.192 0.24 0.14 0.68 0.21 7 0.07914.6 0.1142 1.1 0.0026 0.069 12.77 2.91 0.101 0.11 0.06 18.28 0.09 80.0501 5.8 0.0735 1.4 0.0017 0.044 12.18 3.62 0.064 0.06 0.04 29.63 0.059 0.0280 5.9 0.0421 1.4 0.0009 0.027 3.50 4.51 0.039 0.03 0.02 37.000.03 10 0.0152 5.7 0.0240 1.3 0.0005 0.015 1.48 5.87 0.022 0.03 0.02−15.78 0.03 11 0.0110 5.5 0.0160 1.3 0.0004 0.009 18.43 6.97 0.013 0.010.01 46.74 0.01 12 0.0104 4.9 0.0104 1.4 0.0003 0.006 42.21 8.25 0.0090.04 0.02 −126.38 0.03 ** CV = ( Net ⁢ Counts Net ⁢ Counts ) × 100 ,#Based on 30 mCi Rb-82,  * % ⁢ Error = ( HPGE - DC ⁢ or ⁢ CZT ) HPGe × 100

The date in Table 1 were interpreted relative to three exemplary ratiosor limits, designated an alert limit, and expiry limit, and a legallimit. For Sr-82, the values corresponding to these limits for purposesof the experiment 0.002, 0.01, and 0.02 μCi Sr-82 per mCi of Rb-82,respectively. For Sr-85, the values corresponding to these limits forpurposes of the experiment were ten-fold higher than the Sr-82 limits,or 0.02, 0.1, and 0.2 μCi Sr-85 per mCi of Rb-82, respectively. Theten-fold increase corresponds to a maximum ratio of Sr-85/Sr-82 of 10.

Samples were measured with the CZT detector using a 600 secondacquisition. Background radiation was measured before the samples andcorrected automatically by the infusion system for each strontiumactivity calculation. The % CV for the CZT detector data (Sr-82/85) wasdetermined based on net counts and was <4% down to and including theAlert Limit (0.002) or a total Sr-82/85 content of 0.1 μCi and stillonly approximately 8% at a ratio of 0.0003 almost 10-fold lower.

Counting times for the HPGe detector were adjusted to obtain goodcounting statistics with a maximum CV of approximately 6%. The Sr85/82ratio of 1.462 corresponded approximately that of the example Sr/Rbgenerator used for the experiment at the end of its 42-day life startingfrom an initial ratio of <1. The higher proportion of Sr-85 leads tomore counts than for Sr-82 and the lower CVs seen in Table 1.

For the dose calibrator, the reading of each sample was allowed tostabilize for approximately 30 second before recording the result.

The data show that both the dose calibrator and the CZT detector wereable to accurately measure Sr82/85 radioactivity levels down to belowthe Expiry Limit (ratio 0.01). However, whereas the CZT detector stillexhibited an acceptable error down to a ratio of 0.0004 the DoseCalibrator exhibited unacceptable error at 0.0017, just below the AlertLimit, under the experimental conditions used. Any apparent errors inthe readings provided by the CZT detector were uniform down to thesecond lowest sample but all positive, which suggests good precision butinaccuracy due to insufficient calibration. The errors of the dosecalibrator were larger at lower levels and both positive and negative,suggesting accuracy at higher levels but a lack of precision at lowerlevels.

The data show that the CZT detector made precise measurements down toradioactivity levels well below those encountered at the Alert Limitwhile the dose calibrator lacked precision at radioactivity levels at orlower than the Alert Limit. This is consistent with counting statistics(indicating that sufficient counts are being recorded to achieve adesired precision). A dose calibrator may have a limited measurementresolution of only 0.01 μCi. This is typically caused by the resolutionof the display, which cause rounding or truncation errors. Independentof and additive to any inherent uncertainty in the measurement, theminimum change that can be registered with dose calibrators exhibitingsuch precision for a total Sr-82/85 dose of 0.06+0.01 μCi at the AlertLimit for 30 mCi Rb-82 is plus or minus 17%.

The data show that the CZT used in the example was more precise than thedose calibrator at Sr-82/85 levels encountered near the Alert Limit.

The invention claimed is:
 1. An infusion system comprising: a frame thatcarries a beta detector, a gamma detector, an eluate-receivingcontainer, and a waste container and is further configured to receive aradioisotope generator that generates radioactive eluate via elution,wherein the beta detector is positioned to measure beta emissionsemitted from the radioactive eluate, and the gamma detector ispositioned to measure gamma emissions emitted from a portion of theradioactive eluate received in the eluate receiving container toevaluate a safety of the radioactive eluate delivered by the infusionsystem to ensure that the radioactive eluate generated by theradioisotope generator is safe for patient infusion.
 2. The infusionsystem of claim 1, further comprising an infusion tubing line configuredto receive the radioactive eluate, either directly or indirectly, fromthe radioisotope generator, when the radioisotope generator is receivedby the frame.
 3. The infusion system of claim 2, wherein theeluate-receiving container is in fluid communication with the infusiontubing line to receive the portion of the radioactive eluate, therebyproviding a static portion of radioactive liquid for evaluation by thegamma detector.
 4. The infusion system of claim 3, wherein the betadetector is positioned to measure beta emissions emitted fromradioactive eluate flowing through the infusion tubing line; and thegamma detector is positioned to measure gamma emissions emitted from theportion of radioactive eluate received by the eluate-receivingcontainer.
 5. The infusion system of claim 3, wherein theeluate-receiving container comprises a vial, the infusion tubing linecomprises a needle at its end, and the needle on the infusion tubingline is inserted into the vial.
 6. The infusion system of claim 3,wherein infusion tubing line is part of an infusion tubing circuit thatincludes an eluate line, a waste line, and a multi-way divergence valve,when the radioisotope generator is received by the frame, the infusiontubing line is in fluid communication with the eluate line via themulti-way divergence valve and the waste line is in fluid communicationwith the eluate line via the multi-way divergence valve, the infusiontubing line is connected to the eluate-receiving container, and thewaste line is connected to the waste container.
 7. The infusion systemof claim 3, further comprising a cabinet structure housing at least theradioisotope generator, the infusion tubing line, the eluate-receivingcontainer, the beta detector, and the gamma detector.
 8. The infusionsystem of claim 7, wherein the cabinet structure has a top surfacehaving an opening formed therein through which the eluate-receivingcontainer is configured to be removed and inserted.
 9. The infusionsystem of claim 8, wherein the cabinet structure has a door configuredto selectively open and close to provide access to the eluate-receivingcontainer.
 10. The infusion system of claim 9, wherein the door isconfigured to open upwardly with respect to gravity.
 11. The infusionsystem of claim 1, further comprising the radioisotope generatorreceived by the frame.
 12. The infusion system of claim 11, wherein theradioisotope generator is a strontium-rubidium radioisotope generatorconfigured to generate radioactive eluate containing rubidium-82 viaelution of a column containing strontium-82.
 13. The infusion system ofclaim 1, further comprising a controller in electronic communicationwith the gamma detector, wherein the controller is configured todetermine an activity of strontium in the portion of radioactive eluatebased on the gamma emissions measured from the portion of radioactiveeluate.
 14. The infusion system of claim 13, wherein the controller isconfigured to determine an activity of at least one of strontium-82 andstrontium-85 in the portion of radioactive eluate and evaluate thesafety of the radioactive eluate based on the determined activity. 15.The infusion system of claim 14, wherein the controller is configured toprevent a patient infusion procedure if the determined activity of atleast one of strontium-82 and strontium-85 exceeds an allowable limit.16. The infusion system of claim 13, further comprising a touchscreen incommunication with the controller.
 17. The infusion system of claim 1,further comprising radioactive shielding surrounding the beta detector,the gamma detector, and the radioisotope generator, when theradioisotope generator is received by the frame, the radioactiveshielding providing a barrier effective to reduce radiation emitted bythe radioisotope generator and the radioactive eluate below a limitallowable for operating personnel.
 18. The infusion system of claim 17,wherein the radioactive shielding comprises a shielding assembly havinga plurality of compartments, including a compartment containing the betadetector, a compartment containing the gamma detector, and a compartmentcontaining the radioisotope generator.
 19. The infusion system of claim18, wherein the frame carries the beta detector and the gamma detectorand also receives the radioisotope generator by supporting the shieldingassembly which, in turn, is configured to contain the beta detector, thegamma detector, and the radioisotope generator.
 20. The infusion systemof claim 1, wherein the radioisotope generator, the beta detector, andthe gamma detector are not positioned in a same plane either verticallyor horizontally to maximize a distance between the radioisotopegenerator and the gamma detector.
 21. The infusion system of claim 1,wherein the gamma detector is positioned at a higher elevation than theradioisotope generator and the beta detector is positioned between theradioisotope generator and the gamma detector, when the radioisotopegenerator is received by the frame.
 22. The infusion system of claim 1,wherein the eluate-receiving container is positioned over the gammadetector.